General and Synthetic Methods Volume 2

A Review of the Literature Published During 1977

By G. Pattenden

The Royal Society of Chemistry

Copyright © 1979 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-910-0

Contents

Chapter 1 Saturated and Unsaturated Acyclic Hydrocarbons By J. Fairhurst, D. C. Harwell, and D. E. Tupper, 1,
Chapter 2 Aldehydes and Ketones By S. M. Roberts, 30,
Chapter 3 Carboxylic Acids and Derivatives By D. W. Knight, 67,
Chapter 4 Alcohols, Halogeno-compounds, and Ethers By R. C. F. Jones, 112,
Chapter 5 Amines, Nitriles, and Other Nitrogen-containing Functional Groups By E. F. V. Scriven, 141,
Chapter 6 Organometallics in Synthesis,
Chapter 7 Saturated Carbocyclic Ring Synthesis By M. Mellor and G. Pattenden, 198,
Chapter 8 Strategy and Design in Synthesis By S. Turner, 232,
Reviews on General Synthetic Methods By G. Pattenden, 245,
Author Index, 250,

CHAPTER 1

Saturated and Unsaturated Acyclic Hydrocarbons

BY J. FAIRHURST, D. C. HORWELL, AND D. E. TUPPER

1 Introduction

The Report this year is intended to highlight the new synthetic techniques involved in the formation of saturated and unsaturated hydrocarbons, rather than to describe their reactions which lead to additional or alternative functionality. The trends in synthesis in these areas are towards the use of milder reagents to minimize side reactions and towards the application of organometallic reagents in the regio- and stereo-selective formation of unsaturated moieties found in natural products, particularly amongst the terpenoids.

2 Saturated Hydrocarbons

Jackson and co-workers have described a reductive dehydroxylation technique that can be carried out in the presence of a ketone, e.g. the conversion (1)->(2).

Thus, the chloroformates of primary and secondary alcohols, prepared by reaction of the alcohol with phosgene, are reduced to the corresponding alkane in excellent yield on reaction with tri-n-propylsilane in the presence of t-butyl peroxide at 140°C; yields are low for aryl and benzyl alcohols. A method for the direct replacement of the hydroxy-group of alcohols by alkyl or aryl groups has been described (see Scheme 11, ref. 67).

In a series of papers, Caubere and co-workers have described their continued exploration of the use of ‘complex reducing agents’ in the selective reduction of functional groups. For example, the readily prepared NaH-ButONa-FeCl3 reduces oct-1-ene to n-octane in 90 — 95% yield, and shows selectivity towards exocyclic double bonds. 3 Aliphatic and aromatic halides are reduced to hydrocarbons in high yield by the same reagent, but ketones are unaffected.

Chiral rhodium complexes have found popularity recently in the asymmetric reduction of double bonds bearing polar substituents. However, their application to the asymmetric reduction of hydrocarbon double bonds is limited by their insolubility in non-polar media. Achiwa describes a lipid-soluble complex ‘CPPM-rhodium’, which consists of two biphosphines as metal ligands and a third lipid-solubilizing group, N-cholesteryloxycarbonyl. Thus, a homogeneous solution of CPPM-rhodium in the olefin (3) gives a quantitative yield of the S-hydrocarbon (4) in 24.7% optical yield. Higher optical yields (<60%) are claimed with the d-trans- 1,2-bis (diphenylphosphinoxy) cyclopentanerhodium complex.

Apparently, halogeno-transition-metal complexes supported on phosphine-modified silica carriers are more active than their homogeneous counterparts by a factor of 2 — 4 orders of magnitude, as measured by their effectiveness on the hydrogenation of cyclohexene.

A new synthetic method for the formal addition of alkanes to olefins has been devised. The alkyl mercuric salt (5) reacts with sodium borohydride in the presence of electron-deficient olefins (6) to form the adduct (7). The yield depends on the mode of addition of NaBH4, the temperature, and the salt :olefin ratio.

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A novel reaction scheme, which in effect makes available the hitherto unattainable transformation {8}->{9}->(10), has been realized using an organoarsenic group as a halogen equivalent (Scheme 1). Here, the halogen atom is replaced by a diphenylarsane oxide (11), effecting the conversion (11)->{12) in 67% yield, leaving the halogen atom intact for further synthetic elaboration. Diphenylvinylarsane has been used to effect a two-carbon chain elongation of lithioalkanes to the corresponding alkyl halides. Alkylhydrazines are oxidized by iodine to give mixtures of alkanes, alkyl iodides, alkenes, and alcohols, depending upon the media and base used. Although yields of alkyl iodides can be good in non-aqueous solvents with a weak base, the yields of alkanes are poor. Trialkylboranes react readily with nitrogen trichloride to give the corresponding alkyl chlorides, 13 and PCl3–DMF has been described as a simple ‘brew’ for converting primary alcohols into alkyl chlorides.

Diarylmethanols and triarylmethanols are reduced in high yield to the corresponding methanes by NaBH4 in trifluoroacetic acid. Kabalka and co-workers have now extended the use of catecholborane to effect regiospecific deuterium incorporation via the reduction of tosylhydrazones to the corresponding methylene derivatives.

3 Olefinic Hydrocarbons

Reviews have appeared on the use of the Wittig reaction in industrial practice, the Claisen rearrangement, 18 synthetic applications of the retro-Diels–Alder reaction, organo-palladium intermediates for the alkylation and arylation of olefins, the Prins reaction to give 1,3-dienes, and intramolecular [4 + 2] (Diels–Alder) and [3 + 2] cycloadditions. An interesting discussion of the regiospecificity of the Diels–Alder reaction in terms of frontier orbital overlap favours the Woodward–Katz concept. Useful alkyne and polyene coupling reactions are described in reviews on the chemistry of vitamin D,24 the synthesis of insect sex pheromones, and marine natural product chemistry. The polymerization and copolymerization of buta-1,3-diene have also been reviewed.

New fragmentation and elimination processes are being developed, leading to milder reaction conditions for olefin formation. A novel fragmentation of 1-trimethylsilyloxybicyclo[n,1,0]alkanes (13) with lead tetra-acetate affords the terminal olefinic acids (14) by oxidative cleavage of both cyclopropane bonds ‘a’ and ‘b’ as depicted in Scheme 2. Trost has reported the first case of carbon serving as a leaving group in a Grob fragmentation of (16) in the stereospecific double chain extension reaction, outlined in Scheme 3, providing (17) from (15) in 85% yield. White has now extended his extrusion reaction by developing routes to a range of sulphoximino-3-amino-2-oxazolidones (18), which on mild thermolyses (<140 °C) undergo syn-elimination to give olefins (Scheme 4). A new mild procedure leading to olefins in good yield has been made available by decarboxylative dehydration of β-hydroxycarboxylic acids (19), utilizing the triphenylphosphine–ethyl azodicarboxylate reagent. 32 Compounds (19) are produced by condensing the dilithium salts of carboxylic acids with carbonyl compounds (Scheme 5).

A convenient synthesis of terminal olefins, which may complement the Wittig reaction, has been reported. The procedure (Scheme 6) involves the addition of a carbon nucleophile, derived from a Grignard or alkyl-lithium reagent, to Eschenmoser’s salt. Thermolysis of the derived amine oxide then gives the olefin by Cope elimination in high overall yield. Boyd has detailed his work on nitrone eliminations, analogous to the Cope amine oxide reaction, which gives olefins and oximes as products.

Reetz has shown that hydride acceptors (e.g. triphenylmethyl tetraftuoroborate) may effect elimination of β-hydrogen atoms from organolithium and magnesium compounds, to generate olefins under mild conditions. Yields increase from primary through to tertiary metallated compounds. Furthermore, addition of alkyl- lithium reagents to activated olefins (e.g. 1,1-diphenylethylene) followed by hydride abstraction gives the 2alkyl-1, 1-diphenylalkenes.

Lythgoe and Waterhouse have found that β-hydroxysulphide-S-methyldithiocarbonates (22), chlorosulphides (24), and β-hydroxythiobenzoate sulphones (27) undergo smooth elimination, using tributyltin hydride, via a radical mechanism, to give olefins in good yield. For example, cholestan-3-one (20) may be converted regioselectively into the olefin (21), α-phenylthio-acids (23) into the phenylpenta-1,4-diene (25), and n-heptaldehyde (26) into trans-pentadec-7-ene (28), respectively. Barton describes, in the mechanistically related reaction, that the same reagent converts bisdithiocarbonates of vic-diols into the corresponding olefins in high yields. 38 Both radical eliminations obviate rearrangements of carbonium ion intermediates observed in corresponding acid-catalysed β-eliminations.

Hudrlik has now extended his previous work with Peterson, on the ‘silicon equivalent’ of the Wittig reaction, to the first general method of preparing a variety of heteroatom-substituted olefins, such as vinyl bromides, enol acetates, enol ethers, and enamides. The route is based on the previously described regio- and stereo-specific acid-catalysed ring-opening reactions of α, β-epoxysilanes, followed by stereospecific β-elimination of the resulting β-hydroxysilanes. Other stereospecific deoxygenations of epoxides reported this year to give olefins include those effected by dimethylphenylsilyl-lithium, 2-methyl-2-selenoxobenzothiazole, and, stereoselectively, by pentacarbonyliron; all result in good yields.

Sodium phenylselenoate has been used to convert primary lactones into the corresponding ω-olefinic esters (Scheme 7). Other synthetically useful elimination procedures leading to olefins include Posner’s conclusive studies on the use of neutral, highly active, Woelm Alumina on steroidal sulphonate esters; Marshall’s completed studies on the reduction-elimination of cyclic phosphates, which complements the hexachlorotungstate deoxygenation procedure of Sharpless; and the thermolysis of p-chlorophenyl vinyl sulphoxide Michael condensates with anionic reagents (Scheme 8). A limitation of the reductive elimination of vic-dinitro-compounds by sodium sulphide to olefins is that other readily reducible groups are not well tolerated. Kornblum has now found that calcium amalgam effects the transformation well, even in the presence of esters and nitriles, to give symmetrical and unsymmetrical olefins (Scheme 9).

The ene reaction can effect isomerization of double bonds to positions not readily accesible by other means. Two interesting papers describe the use of chloral as an enophile in reactions with 1,1- and 1,2-dialkyl-substituted ethylenes, to give the ene adduct in good yields [(29}->(30)]. Asymmetric induction of the ene reaction of chloral with (–)-β-pinene gives a 17:3 mixture of the two diastereoisomers (31) and (32), but in the presence of Lewis acids the ratio is considerably altered, titanium tetrachloride giving (31) 100% stereoselectively! This promising result indicates that, in principle, if the part of the molecule derived from the enophile can be detached without loss of chirality, the ene component can be recycled, thus acting as a chemical ‘template’. An apparently novel ‘polar equivalent’ of the ene reaction has been recognized in the base-induced conversion of the anion of 3,7-dimethylocta-1,6-diene into the allylic carbanion of 1,2-dimethyl-3-isopropenylcyclopentane. Ene reaction of sulphur dioxide with exocyclic methylene bonds provides an easy method for the regiospecific isomerization of olefins [e.g. (33}->(34)]. Perhaps more useful is Nsulphinylbenzenesulphonamide (PhSO2N=S=O) which will also isomerize endocyclic to exocyclic methylenes. Barton has found that rhodium trichloride trihydrate is an effective catalyst for difficult exocyclic to endocyclic double-bond isomerizations [e.g. (35)->(36)].

Diethyl azodicarboxylate will participate in the ene reaction with both cyclonona-1,2-dienes and acyclic allenes to give the corresponding 2-ylbicarbamate-1,3-dienes under mild conditions and in good yields. A study of the reactivity of diene (37) with activated olefins indicates that the percentage of ene adduct (38) over the Diels-Alder product (39) increases with a more highly substituted olefin.

Azo-dienophiles give more ene adduct than the corresponding substituted carbodienophile. The spirosesquiterpenoids (±)-β-acorenol, (±)-β-acoradiene, (±)-acorenone-B, and (±)-acorenone have all been synthesized from the ester (40). The key step, as previously described for the β-acorenol synthesis, is the 100% endo-selective intramolecular ene reaction of the 1,6-diene (41) to a mixture of the epimers (42a and b).

Additions of organometallic reagents to 1-alkynes continue to play a prominent role in the regio- and stereo-selective synthesis of olefins. A convenient procedure for the stereospecific synthesis of trisubstituted olefins, based on Normant’s work on the addition of alkyl copper(I) complexes to 1-alkynes, is outlined in Scheme 10. The use of House’s dimethyl sulphide-copper(I) bromide complex minimizes 1,3-diene formation by stabilization of the intermediate vinylcopper(I) complex (43). Westmijze and Vermeer have now extended the use of the addition of vinyl copper(I) complexes to 1-alkynes in an apparently general route to 1-alkenyl halides, nitriles, sulphides, phosphines, and tin compounds. Normant has found that heterosubstituted alkynes also react regio- and stereo-selectively. (E)-Alkenylarenes may also be synthesized in high yield by the [Ni(PPh3)4]-catalysed reaction of aryl iodides or bromides with (E)-alkenyl zirconium compounds, derived from 1-alkynes, and the Schwartz reagent [Cl(H)ZrCp2].

The ligand attached to palladium(II) complexes has been shown to be critical in determining the yields of the anti-Markovnikov addition of methyl-lithium to styrene. The yield of product, β-methylstyrene, increases in the ligand order Cl(3% )E)-olefins from alkenyldialkylboranes.

A possibly new method for the direct substitution of the hydroxy-group of both saturated and unsaturated alcohols with alkyl or aryl groups has been devised. The alkyl- or aryl-lithium, via the mixed cuprates, replaces the hydroxy-group regio- and stereo-selectively in high yields in the presence of [Ph3PN(CH3)Ph]+I- . Particular applications are exemplified by the n-butylation of the alcohol (44) to give a 91: 9 mixture of the olefins (45) and (46), in 80% yield, and also by the allylation of geranyl alcohol (47) to give the 1,5-diene (48) with complete regioselectivity (Scheme 11).

The massive synthetic potential of the olefin metathesis reaction has yet to be realized in terms of generality and yields. However, since the metallocarbene addition mechanism has been largely accepted, more useful mechanistic studies have appeared this year. The whole area has been adequately reviewed by the timely publication of the proceedings of the international symposium held at Noordwi jkerhout in September 1977. The synthetic utility of this transformation has now been extended by tungsten catalysis to the functionalized olefins of ω-olefinic esters (49), to give reasonable yields (35 — 40%) of the products as isomeric mixtures (50) in which the trans-isomer predominates. Small amounts of the chlorinated starting materials (51) are also present. The complex tungsten catalyst [Ph2C=W(CO)5] appears to maintain a higher stereospecificity than other catalyst systems, even with acyclic olefins such as cis-pent-2-ene.

Organometalloids containing sulphur, boron, silicon, and selenium continue to demonstrate their versatility as synthons used to introduce allyl or vinyl functionality stereoselectively. The trialkylvinylborate complex (52) is conveniently prepared from trialkylborane and vinylmagnesium bromide. On treatment with aqueous alkali followed by oxidation with iodine, the complex readily gives the corresponding 1-alkenes (53). Treatment of the boracyclopent-3-enes (54) (available by a photolytic procedure on hydroboration of the iodo-enyne) with acetic acid followed by peroxide oxidation offers an intriguing new stereoselective sequence to homoallylic alcohols (Scheme 12). Brown now describes how, unlike their saturated counterparts, the unsaturated B-alkenyl-9-borabicyclo[3,3,1]nonanes (B-alkenyl-9-BBN) add to the carbonyl group of simple aldehydes to effect a ‘Grignard-like’ stereospecific route to trans-allylic alcohols.

(Continues…)Excerpted from General and Synthetic Methods Volume 2 by G. Pattenden. Copyright © 1979 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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General and Synthetic Methods Volume 10

A Review of the Literature Published in 1985

By G. Pattenden

The Royal Society of Chemistry

Copyright © 1988 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-914-8

Contents

Chapter 1 Saturated and Unsaturated Hydrocarbons By N. Simpkins, 1,
Chapter 2 Aldehydes and Ketones By K.E.B. Parkes, 32,
Chapter 3 Carboxylic Acids and Derivatives By D.W. Knight, 75,
Chapter 4 Alcohols, Halogeno-compounds, and Ethers By L.M. Harwood, 187,
Chapter 5 Amines, Nitriles, and Other Nitrogen-containing Functional Groups By S.G. Lister, 230,
Chapter 6 Organometallics in Synthesis By S.G. Davies and T. Gallagher, 320,
Chapter 7 Saturated Carbocyclic Ring Synthesis By T.V. Lee, 416,
Chapter 8 Saturated Heterocyclic Ring Synthesis By K. Cooper and P.J. Whittle, 457,
Chapter 9 Highlights in Total Synthesis of Natural Products By K.E.B. Parkes and G. Pattenden, 550,
Reviews on General and Synthetic Methods Compiled by K. Carr, D.J. Coveney, and G. Pattenden, 596,
Author Index, 604,

CHAPTER 1

Saturated and Unsaturated Hydrocarbons

BY N. SIMPKINS

A catalyst comprising fused iron promoted by V2O5 is extremely efficient in the gas-phase hydrodeoxygenation of ketones and alcohols at relatively low pressures. Reductive d ecyanation of a variety of nitriles can be accomplished very cleanly using potassium metal in combination with a crown ether. The use of ultrasound allows for short reaction times in the reaction of gemdihalogenopropanes with various metals to form the usual carbenoid-derived products. The reduction of C-C multiple bonds has been found to take place in the presence of platinized TiO2 under illuminated conditions. A variety of unsaturated substrates react, although the reaction times are q uite long (ca. 26 h). A useful method for conjugate reduction of α,β-unsaturated ketones and aldehydes involves reaction with diphenylsilane catalysed by Pd0 in combination with ZnCl2. Excellent yields of reduced compounds were obtained using this method, which does not affect α,β-unsaturated nitriles or esters (Scheme 1).

The use of a trialkylaluminium-alkylidene iodide mixture to effect cyclopropanation has been re-examined. The reaction was found to work well when conducted in CH2Cl2, and shows contrasting regioselectivity to the Simmons-Smith reagent in reaction with geraniol (Scheme 2).

A new method which allows enantioselective cyclopropanation of α,β-unsaturated aldehydes employs acetals derived from tartrate esters. The method appears operationally straightforward and gives good yields and enantiomeric excesses (e.e.) (Scheme 3).

2 Olefins

Sodium borohydride can now be used for the reduction of acetylenes, by employing a NaBH4-PdCl2-polyethylene glycol-CH2Cl2 system. A variety of reduced products were obtained including cis-olefins and fully reduced materials.

The use of transition metal catalysts for dehydrogenation of alkanes has received more attention. The iridium complex [(Pri3P)2IrH5] exhibits unusual selectivity for this type of reaction in that methyl groups are attacked preferentially. Similarly, a photolytic dehydrogenation reaction was observed using [IrH2(CF3CO2)(PR3)2], even in the absence of the usual hydrogen acceptor t-butylethylene.

The reductive removal of allylic oxygenated functions can be carried out effectively using nickel boride. Allylic alcohols and their silyl ethers react , although they require much longer reaction times than the corresponding acetates (Scheme 4). Another new deoxygenation procedure constitutes the latest conversion of epoxides into the corresponding olefins, and utilizes arylseleno-carboxamides. The method is stereospecific (retention) although it requires the presence of a strong acid (CF3CO2H) and does not convert more sterically hindered epoxides such as norbornene oxide.

Luche has reported the reaction of carbonyl compounds with allylic halides in aqueous media. The reaction can be performed using either zinc or tin, and displays good chemoselectivity between aldehydes and ketones (Scheme 5).

Asymmetric coupling of aryl Grignards with allylic pivalates is possible in good e.e. by use of NiCl2[(S,S)-chiraphos] in only catalytic (1 mol%) amounts. Another allylic coupling reaction uses palladium to mediate displacement of an acetoxy-group from an allylic geminal diacetate by a sta bilized nucleophile, e.g. Scheme 6. Depending upon the substituents present on the reacting partners, the regioselectivity alters and a variety of products can be prepared.

A number of allylated and related products having quaternary carbon atoms may be prepared by radical chemistry starting from tertiary alcohols.

Allylstannanes have been prepared in a regioselective fashion by a selenoxide elimination route, and also via direct metallation of hydrocarbons. The latter procedure when combined with a protodestannylation step enables isomerization of various terpenes, e.g. Scheme 7.

A number of reports have focused interest on the synthesis of various allylic sulphur compounds. A one-pot procedure for the preparation of allylic sulphides from the corresponding alcohols involves initial rearrangement of the xanthate followed by extrusion of COS (Scheme 8). Allylic sulphides and sulphones are available from the corresponding nitro-compounds. Thus (1) on treatment with NaSPh in HMPA gave the sulphide (2), whereas the sulphone (3) was produced by reaction of (1) with PhSO2Na in DMF in the presence of [Pd(PPh3)4] (Scheme 9). Although the contrasting regioselectivity of the reactions is interesting, the products are perhaps more readily available by other methods [e.g. in the case of (3) by alkylation of the allylic sulphone anion]. Another research group has published similar chemistry starting from vinyl nitro-compounds. Warren et al. have published more chemistry leading to allylic (and also vinylic) sulphides, utilizing both β-hydroxy-sulphides and allylic phosphine oxides. Other applications of the phosphine oxide chemistry to the preparation of allylic products have also appeared. Vinyl sulphides have also been prepared by benzyne-induced fragmentation of 1,3-oxathiolanes and via hydroboration of 1-iodoalkynes (Scheme 10).

Vinyl alkyl selenid es can be prepared from the more readily obtainable vinyl methyl selenides by a d emethylatiolkylation sequence which retains the stereochemistry of the starting materia1. The chemistry of vinylic compounds containing silicon groups have received considerable attention. Acetylenes can be disilylated using a reagent derived from Me3SiLi, MeMgI, and MnCl2. Distannylation can also be achieved. Addition of (trimethylsilyl) trimethylstannane across the triple bond of alk-1-ynes gives products of type (4) in regio- and stereo-specific fashion.

Vinyl nitriles containing silicon groups have been obtained by palladium-catalysed ad dition of TMSCN to acetylenes, and by the addition of HCN to silylated acetylenes mediated by nicke1. The regioselectivity of the copper-catalysed silylzincation of terminal acetylenes described by Oshima can be very effectively controlled by the correct choice of reagent (Scheme 11).

Corey has now published additional details concerning the chemistry of the reagent derived by treatment of methylenetriphenyl-phosphorane with an additional equivalent of alkyl-lithium. The reagent formulated as (7) methylenates even very sterically hindered ketones, and also opens epoxides (Scheme 12). In contrast to this report, Schlosser has provided good evidence for formation of (7) only by halogen-metal exchange of (8), whereas base treatment of methylenetriphenylphosphorane results in ortholithiated species (9) (Scheme 13). This disparity is probably due to differences evident in the reaction conditions used by each group and particularly the temperatures used for the second metallation.

A very direct electrochemical method for the preparation of 1-cycloalkenyltriphenylphosphonium salts has been reported, which uses simple cyclic alkenes and triphenylphosphine as starting materials. Although yields are only moderate, this route should prove the method of choice for preparation of these valuable inter mediates. Salt-free Wittig reaction of 2-oxygenated cyclohexanones exhibits good to excellent Z-selectivity depending on the exact nature of the 2-substituent (Scheme 14).

Amongst the alternatives to phosphorus-based olefination procedures, the use of sulphones remains popular. Thus, fluoromethyl phenyl sulphone has been used to prepare vinyl fluorides via fluoro-α, β-unsaturated sulphones, and an improvement on an earlier methylenation procedure involves alkylation of sulphone anions with R3SnCH2I (Scheme 15). Use of R3SnCH2I rather than its silicon analogue results in a d ramatic increase in the rate of both the alkylation and fragmentation steps. The method was also extended to methylenation of nitriles although somewhat harsher conditions (MeLi, -20 °C) were required for the second fragmentation step as Bu4NF was found to be ineffectual. Sulphones are also used in a new method for the stereoselective preparation of α,β-unsaturated amides. The dianion of the sulphone (10) was sequentially alkylated, and then reacted with NaBH4 to furnish the desired amides (Scheme 16). Reaction of (10) with epoxides was also possible, giving adducts which could be cyclized using KOBut leading to substituted dihydropyrans.

Unsaturated amides and esters are also available by a novel palladium-catalysed carbonylation of enol triflates. This method gave uniformly high yields on a number of steroidal substrates, e.g. Scheme 17.

Wittig and Peterson methodologies have been used for the preparation of α,β-unsaturated thioesters and α-silyl- α,β-unsaturated esters respectively. Selenoxide elimination is well established as a mild method for olefination, selenium usually being introduced into the substrate molecule in its divalent state. The use of phenylselenium trichloride now allows direct introduction of tervalent selenium and enables subsequent conversion into the selenoxide and elimination without the use of an oxidant (Scheme 18). Reduction of the intermediate dichloroselenides to the corresponding selenides was also achieved by reaction with thiourea.

A number of papers have appeared detailing new developments of existing annulation methods which yield cyclic olefins. Danheiser has modified his stereocontrolled [4+1] annulation approach to cyclopentene d erivatives, to accommodate carbon rather than oxygen substitution at C-3 (Scheme 1 9). The key step in the sequence is the carbanion-accelerated vinylcyclopropane-cyclopentene rearrangement which appears quite efficient. Unfortunately the rather poor yields in the initial steps of the sequence and the lengthy nature of the overall procedure detract somewhat from its appeal. Posner has developed a convenient one-pot, three-component construction of cyclohexenes which involves two consecutive Michael additions followed by a ring closure reaction, e.g. Scheme 20.

Fragmentation reactions of cyclic substrates containing silicon or tin provide a useful route into functionalized acyclic olefins. Wilson has developed the CeIV-mediated oxidative fragmentation of γ-hydroxy-silanes which affords fair yields of δ,ε-unsaturated aldehydes or ketones. Cyclic β-stannyl-oximes fragment similarly when treated with lead tetra-acetate, leading to either acyclic or ring-contracted products (Scheme 21). Both this and another study indicate that such fragmentations occur with efficient translation of stereochemistry into the olefinic products. A cyclopropane-opening carbonylation reaction gives good yields of γ,δ-unsaturated carboxylic acid derivatives (Scheme 22). The reaction offers a method of regioselective carboxylation of an allylic alcohol or halide [the precursors to cyclopropanes (11)], but has the disadvantage of using 3-6 equivalents of [Ni(CO)4].

3 Conjugated 1,3-dienes

Taylor has nicely controlled the double carbocupration reaction of organocuprates with acetylenes to provide a general entry to Z,Z-dienes, e.g. Scheme 23. After treatment of the dialkylcuprate with acetylene (initially at -50 °C and then at 0 °C) the reaction can be quenched with a variety of electrophiles (RX, enones, CO2, etc.) to give the Z,Z-products stereospecifically.

Terminal conjugated (E) dienes and trienes are available by SnCl2-mediated reaction of an aldehyde with 1-bromo-3-iodo-propane, e.g. Scheme 24. The procedure is operationally simple, and is chemoselective in that ketones are unreactive. Corey has used the amino-ylide (12) to convert the hindered aldehyde (13) into the Z-homoallylic amine (14). Subsequent Cope elimination then furnished the Z,E diene (Scheme 25).

Cyclic dienes are available by tellurolate 1,4-elimination of 1,4-dibromo-2-enes, and also by a new annulation sequence involving intra molecular Pd-catalysed reaction of an enol triflate with a vinylstannane appendage (Scheme 26).

A variety of polysubstituteq dienes have been synthesized using a very high yielding sequence starting from α,α’-diketo-sulphides (Scheme 27). Even very heavily substituted dienes can be made in this way, the products being formed stereoselectively in certain cases.

Trost has described a new palladium(2+)-catalysed ene-type cyclization which furnishes either 1, 3- or 1 ,4-dienes. This method utilizes enynes such as (15) as starting materials, which themselves are readily available by previous Pd technology (Scheme 28). The method tolerates a variety of other functionality in the molecule, and both the enyne synthesis and subsequent cyclization can be combined in a one-pot procedure if desired.

Cyclization of aromatic enynes such as (16) to give vinyl-phenanthrenes occurs on exposure to metal carbenes, e.g. R1R2=W(CO)5 (Scheme 29). The intermediate metallocenes of type (17) are proposed to undergo highly selective ring opening to give the products of cis stereochemistry. A number of papers report developments in the palladium- or ruthenium-catalysed coupling of various vinylic substrates with a variety of partners to give dienyl products; some examples are outlined in Scheme 30.

A one-pot synthesis of 1,1-bis(methylthio)alka-1, 3-dienes has appeared, and Wallace has outlined some useful stereoselective routes to various functionalized hexa-2, 4-dienals starting from a readily available cyclobutene. Phenylsulphonylmercuration of 1, 3-dienes, followed by base-promoted demercuration, constitutes a regioselective route to dienyl-sulphones (Scheme 31).

4 Non-conjugated Dienes

Allylic sulphones feature in the oxidative dimerization described by Büchi whereby lithio anions derived from allylic sulphones were treated with either iodine or FeCl3-DMF complex, to provide 1,5-dienyl bis-sulphones, e.g. Scheme 32. As can be seen, complementary isomer distributions were observed for each oxidant.

1,5-Disubstituted Z,Z-penta-1,4-dienes (21) were prepared by the sequence shown in Scheme 33. The method is conceptually similar to the sequence described above (Scheme 23) for Z,Z-1, 3-dienes, although the yields and stereoselectivies are somewhat more modest.

Hexa-1,5-dien-3-ols are obtained (albeit with moderate regio-selectivity) from the reaction between allylic epoxides and tri-alkylalkynylborates (Scheme 34). This selectivity complements the behaviour of various other organometallics (M = Li, MgBr, Zn, etc.) which give predominantly products of type (23). The use of allyloxybenzothiazoles as electrophiles in organometallic coupling reactions has recently been extended to reactions involving allylic Grignards as reaction partners. These reactions show high regio-selectivity, which can be controlled to give 1,5-dienes of type (24) or (25) by appropriate choice of reaction conditions (Scheme 35).

Finally, a contribution from the Trost group describes the intramolecular coupling of an allylic acetate with an in situ generated allylstannane, inevitably catalysed by palladium (Scheme 36 ).

5 Allenes

A series of simple allenes has been prepared by a very straightforward multistep procedure, starting from crotonaldehyde (Scheme 37). Another route to such compounds utilizes the reaction Bu3SnLi and ethers derived from β-phenylsulphinyl-β,γ-unsaturated alcohols (Scheme 38).

Allenic ketones are available by a simple and high-yielding sequence starting from the acetal-aldehyde (26), itself readily available from ethyl pyruvate (Scheme 39).

(Continues…)Excerpted from General and Synthetic Methods Volume 10 by G. Pattenden. Copyright © 1988 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.

General and Synthetic Methods Volume 8

A Review of the Literature Published During 1983

By G. Pattenden

The Royal Society of Chemistry

Copyright © 1986 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-894-3

Contents

Chapter 1 Saturated and Unsaturated Hydrocarbons By J. M. Clough and C. R. A. Godfrey, 1,
Chapter 2 Aldehydes and Ketones By S. C. Eyley, 84,
Chapter 3 Carboxylic Acids and Derivatives By D. W. Knight, 131,
Chapter 4 Alcohols, Halogeno-compounds, and Ethers By L. M. Harwood, 200,
Chapter 5 Amines, Nitriles, and Other Nitrogen-containing Functional Groups By S. G. Lister, 245,
Chapter 6 Organometallics in Synthesis, 312,
Chapter 7 Saturated Carbocyclic Ring Synthesis By T. V. Lee, 381,
Chapter 8 Saturated Heterocyclic Ring Synthesis By K. Cooper and P. J. Whittle, 407,
Chapter 9 Highlights in Total Synthesis of Natural Products By K. E. B. Parkes and G. Pattenden, 497,
Reviews on General and Synthetic Methods By G. Pattenden and G. M. Robertson, 541,
Author Index, 548,

CHAPTER 1

Saturated and Unsaturated Hydrocarbons

BY J. M. CLOUGH AND C. R. A. GODFREY

1 Saturated Hydrocarbons

Many new methods for the preparation of alkanes via reductive removal of functional groups have been reported during the year. A preparatively useful method for the conversion of carboxylic acids into alkanes has been developed by Barton and his co-workers. Primary, secondary, and tertiary carboxylic esters (1) derived from thiohydroxamic acids such as N-hydroxypyridine-2-thione undergo efficient radical chain decarboxylation to the corresponding nor-alkanes on treatment with either tri-n-butyltin hydride or t-butylmercaptan. Under these mild reaction conditions, ketones, olefins, and normal carboxylic esters remain unchanged. Decarboxylation of carboxylic acids can also be effected using sodium persulphate and a catalytic amount of silver nitrate. Unstabilized alkyl radicals from aliphatic acids afford alkanes or, in the presence of copper(II) salts, alkenes. By contrast, arylacetic acids give benzylic radicals, and these dimerize to give 1,2-diarylethanes in moderate yields.

Williams and Moore have reported that the reduction of a variety of heterocyclic thiones to the corresponding methylene compounds occurs readily on heating with an excess of tri-n-butyltin hydride and a radical initiator (e.g. Scheme 1). Conversion of the cyclic thiocarbonate (2) into the 1,3-dioxolane (3) is noteworthy in that the Corey–Winter reaction does not take place under the reaction onditions. The desulphurization of thiols and thioketones to alkanes and alkenes using sodium triethylborohydride and iron(II) chloride is improved by adsorption of the borohydride onto alumina. Moreover, this heterogeneous reaction occurs at room temperature and products are easily isolated by simple filtration. A variety of benzylic di- and tri-arylmethyl mercaptans react with stoicheiometric amounts of [Fe3(CO)12] or [Co2(CO)8] under phase-transfer conditions to give the corresponding hydrocarbons in good yields.

Monosubstituted thiiranes are reduced to alkanes on treatment with Raney nickel in ethanol at –40°C, conditions under which olefinic bonds are unaffected.

On irradiation, solutions of diselena[3.3]cyclophanes in HMPA are transformed cleanly into the corresponding cyclophanes (e.g. Scheme 2).

Treatment of (hydroxymethyl)diphenylphosphine oxides (4) with P2I4 in carbon disulphide at room temperature affords excellent yields of the alkyldiphenylphosphine oxides (5) with no trace of the corresponding iodides.

Suzuki and his co-workers have shown that benzyl alcohols are smoothly deoxygenated on treatment with P2I4 in boiling benzene. The reaction works well even with sterically hindered secondary benzyl alcohols, as illustrated in Scheme 3. Extending this work, the same group has reported that a mixture of LiAlH4 and P2I4 offers a mild alternative to conventional methods for the deoxy-genation of aromatic ketones (e.g. Scheme 4). Halogens, esters, and olefinic bonds are not affected by these reaction conditions.

Ueno and his co-workers have described conditions under which tosylates, including those derived from primary alcohols, undergo efficient radical deoxy-genation to give hydrocarbons. A noteworthy example is the selective removal of the tosyl group from the diol derivative (6) which takes place without the need to protect the free hydroxy-group.

Several reports describing the use of lithium triethylborohydride for the reduction of alkyl halides, especially alkyl fluorides, have been published during the year. Catalytic amounts of silver perchlorate markedly accelerate the reduction of 1,1-dibromocyclopropanes to the corresponding monobromides by LiAlH4. This catalyst also facilitates the reduction of tertiary or sterically hindered alkyl bromides which are normally resistant to LiAlH4. gem-Bromochloro-cyclopropanes react with a mixture of diethyl phosphonate and triethylamine to give the corresponding chlorocyclopropanes exclusively, and (trichloromethyl)-benzene is reduced to (dichloromethyl) benzene in a yield of 86% under the same conditions. Photostimulated reduction of either cyclohexyl chloride or bromide with LiAlH4 in the presence of di-t-butyl peroxide gives cyclohexane in good yield. Vinyl bromides are converted into olefins under these conditions, but yields are only moderate. α-Halogenocarbonyl compounds are smoothly dehalogenated on treatment with sodium hydrogen telluride, generated in situ from tellurium and NaBH4 in ethanol.

α-Nitrohydrazones (7), readily prepared from the corresponding nitroalcohols (8), are cleanly reduced to the hydrazones (9) on treatment with LiAlH4. However, the reaction fails for nitrohydrazones (7) in which R2 and R3 are both hydrogen atoms.

Dimeric products often encountered during the reduction of nitroalkenes to the corresponding nitroalkanes with NaBH4 can be avoided by carrying out the reaction at 25°C in the presence of silica gel, in a mixture of chloroform and propan-2-ol. Reasonable yields of alkanes can be obtained by electrohydrogenation of both alkenes and alkynes using a nickel-plated cathode coated with Raney nickel powder. However, many other functional groups are also reduced under these conditions.

Alper and Heveling have reported the first examples of organometallic phase-transfer catalysis under acidic conditions. For example, hydrogenation of 9,9′-bifluorenylidene (10) or diarylethylenes occurs on treatment with [Co2(CO)8] or [Co2(CO)6(PBu3)2] and tetrafluoroboric acid under phase-transfer conditions. Anthracene, however, is not reduced. The solvated ion pair [(C8H17)3NMe]+[RhCl4]- catalyses the hydrogenation of a variety ofonsaturated compouds under phase-transfer conditions. Even aromatic substrates may be reduced to the corresponding alkanes at room temperature and under a pressure of 2 atm of hydrogen, but reaction rates are sensitive to steric effects.

Reactive halides such as benzyl bromide undergo homo-coupling on treatment with titanocene methylene–zinc halide complexes of the type [Cp2TiCH2.ZnX2](X=Cl or I).

Reetz and Westermann have reported that treatment of lithium alkoxides of the type (11) with a 1:1 mixture of MeTiCl3 and Me2TiCl2 at –40°C affords the methylated products (12), which are potentially useful as synthetic tetra-hydrocannabinoid intermediates. Undesirable Wagner–Meerwein rearrangements or retro-Friedel–Crafts reactions are not observed under these reaction conditions. By contrast, gem-dimethylation of the optically active disubstituted cyclopentanone (13) using Me2TiCl2 affords a mixture of racemic cuparene (14) and the olefin (15), products which can be accounted for in terms of intermediate carbonium ions.

2 Olefinic Hydrocarbons

Although the extremely hindered olefin tetra-t-butylethylene has still not been synthesized, the closely related compounds (16), (17), (18), and (19) have been prepared and characterized, and some of these are potential precursors of tetra-t-butylethylene itself.

House and his co-workers have synthesized further examples of strained enones, either by elimination or by intramolecular Wadsworth–Emmons reactions. 2-Phenylbicyclo[3.3.1]non-1-en-3-one (20) is stable when protected from oxygen, or nucleophiles such as water. By contrast, the bicyclo[3.2.1]octane species (21) and (22) could only be generated as transient intermediates which were trapped with nucleophiles or, in the case of (22), as a cycloadduct with furan. A simple two-step preparation of bicyclo[3.3.0]oct-1-en-3-one also makes use of an intramolecular Wadsworth–Emmons reaction (potassium carbonate and 18-crown-6 in benzene at 60°C) to close the second ring.

Bicyclo[5.1.1]non-1(8)-ene (23) has been synthesized by Ramberg–Bäcklund reactions using each of the stereoisomeric bromosulphones (24) and (25) (Scheme 5). No competing 1,2-dehydrobromination is observed. Although isolable, the olefin (23) shows the usual high reactivity towards oxygen, acids, and dienes. Another way of constructing bridgehead olefins is via intramolecular Diels–Alder reactions, but high temperatures are usually required. Shea and Gilman have now shown that, in the presence of stoicheiometric amounts of diethylaluminium chloride, these reactions take place smoothly at room temperature. A particularly impressive example is the reaction shown in Scheme 6 which gives a 70% yield of the bridgehead olefin within 5 minutes.

Marshall and Flynn have reported that trans-hydroxymethylcycloalkenes [e.g. (26)] of known absolute configuration and high optical purity can be prepared by the Sharpless kinetic resolution procedure. The (+)-(R)-trans-cycloalkene (26) was converted in six steps into (+)-(R)-[10.10]-betweenanene (27) with better than 90% optical purity (Scheme 7).

The low-valent titanocene species generated by reducing [Cp2TiCl2] with sodium naphthalenide is a highly efficient and almost stereospecific catalyst for the isomerization of simple non-functionalized terminal alkenes to (E)-2-alkenes. The transformation is complete within minutes at room temperature and internal olefinic bonds of either configuration are inert under the reaction conditions. Hex-1-ene is rapidly converted into a stereoisomeric mixture of hex-2-enes on treatment with a catalytic amount of the stable and commercially available complex [OsHBr(CO)(PPh3)3] in toluene at 150°C.

Partial hydrogenation of acetylenes to olefins is often accomplished using the Lindlar catalyst. A systematic study with nine metal ions has now shown that the chemoselectivity for semihydrogenation, especially for monosubstituted acetylenes, is significantly and reproducibly improved when the catalyst is modified with manganese(II) chloride. Suzuki and his co-workers have described two new systems for the partial reduction of acetylenes to (Z)-olefins at room temperature. The first, a catalytic amount of palladium chloride in polyethylene glycol and dichloromethane, allows diphenylacetylene to be hydrogenated to (Z)-stilbene at atmospheric pressure, but over-reduction appears to be a problem. Much better selectivity is achieved with the second system in which NaBH4 replaces hydrogen. Simple 1,3-dienes can be hydrogenated specifically to olefins at –78°C using allyl(hydrido)platinum(II) complexes as catalysts.

Oxiranes are conveniently deoxygenated to give olefins using hydrogen iodide generated in situ from toluene-4-sulphonic acid and sodium iodide in acetonitrile. The transformation is complete within minutes at room temperature.

Vinyl sulphones are reduced to the corresponding olefins in high yield and with retention of configuration on treatment with alkyl Grignard reagents and nickel or palladium catalysts in THF at room temperature (e.g. Scheme 8). Coupling products between the sulphone and Grignard reagent are only formed to a small extent (generally <6%) under these conditions. Another new method for the reduction of vinyl sulphones to olefins is illustrated by the examples shown in Scheme 9. Its success stems from the regiospecific 1,4-addition of tributylstannyl-lithium to vinyl sulphones in THF at –78°C, and the instability of the resulting β-tributylstannylsulphones, which collapse to form olefins on treatment with silica gel. A drawback of the method is its lack of stereochemical control, but it does provide a chance to modify the product by treating the intermediate sulphonyl-stabilized anion with electrophiles such as methyl iodide (Scheme 9) or aldehydes (which give allylic alcohols).

Vinylsilanes with a hydroxy-group in the β-position are rapidly desilylated via a homo-Brook rearrangement on treatment with potassium hydride (e.g. Scheme 10).

A sequence for the reduction of a cyclopentenone to the corresponding cyclopentene without scrambling of the position of the olefinic bond has been devised as part of a synthesis of a prostaglandin analogue (Scheme 11).

Tritylpotassium rapidly dehydrohalogenates secondary alkyl bromides and iodides at 0°C to give high yields of olefins. The reagent is less satisfactory with secondary alkyl chlorides and it fails altogether with primary alkyl halides. When solutions of phenethyl or secondary alkyl bromides are treated with 2.5 equivalents of alumina-supported potassium fluoride, smooth dehydrobromination takes place, but without regio- or stereo-control. Under the same conditions, 1,2-dibromides and vinyl bromides are converted into acetylenes, and 2phenoxyethyl bromide gives phenyl vinyl ether.

In contrast to the well-known selenoxide elimination, little has been reported concerning olefin formation by elimination of telluroxides. Uemura and Fukuzawa have now shown that although primary alkyl phenyl telluroxides undergo elimination only at high temperatures, secondary alkyl phenyl telluroxides readily decompose at room temperature to give isomeric mixtures of olefins (e.g. Scheme 12). The use of appropriate precursors allows the reaction to be applied to syntheses of allylic alcohols and allylic and vinyl ethers, and this is of more preparative value since elimination is both regio- and stereo-specific in these cases (e.g. Scheme 13).

On heating in DMSO, 2-cycloalkoxytropones, prepared from cycloalkanols, tropolone, and DCC, undergo stereospecific trans-elimination to give high yields of cycloalkenes. Experiments with deuterium-labelled precursors support the concerted intramolecular mechanism shown in Scheme 14. The analogous tropone derivatives of acyclic alcohols give acyclic olefins under the same conditions, but these are contaminated with ketones derived from the original alcohols.

Reductive debromination of vic-dibromides to give olefins is conveniently conducted using sodium sulphide or sodium hydrogen sulphide under aqueous phase-transfer conditions. Elimination takes place with at least 85% anti-stereoselectivity. A variety of functional groups (hydroxyl, ketone, lactone) tolerate the reaction conditions, but olefinic bonds can migrate into conjugation with carbonyl groups. The same transformation takes place when benzene solutions of vic-dibromides are irradiated with u.v. light in the presence of three equivalents of triethylamine, but generally without stereocontrol. α,β-Dihalogeno-ketones and -esters are converted into α,β-unsaturated ketones or esters under the same conditions. Sodium hydrogen telluride reduces 1-nitro-1-(1-nitrocyclohexyl)cyclohexane, a vic-dinitro-compound, to cyclohex-ylidenecyclohexane in a yield of 86%.

Hindered methyl esters which possess a suitably placed benzylic or allylic bromine atom undergo fragmentation on heating in HMPA to give high yields of olefins (e.g. Scheme 15).

New experimental conditions for the Wittig reaction involve passing an aldehyde in a gaseous state through a heated bed of a phosphonium salt and potassium carbonate. The olefinic product, also a gas under the reaction conditions, is collected, leaving the triphenylphosphine oxide adsorbed on the solid bed. A wide range of aldehydes are suitable, provided they have sufficient volatility, but ketones do not react. Wittig reactions performed with reactive ylides under solid–liquid phase-transfer conditions (potassium carbonate in wet 1,4-dioxane or methanol) allow selective mono-olefination of terephthalic aldehyde or olefination of phenolic benzaldehydes without protection of the phenolic group. Furthermore, Wittig reactions between aldehydes and resonance-stabilized phosphoranes are strongly accelerated if performed under high pressure (10 kbar) and there is also an improvement in the (E)-stereoselectivity.

(Continues…)Excerpted from General and Synthetic Methods Volume 8 by G. Pattenden. Copyright © 1986 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
All rights reserved. No part of this excerpt may be reproduced or reprinted without permission in writing from the publisher.
Excerpts are provided by Dial-A-Book Inc. solely for the personal use of visitors to this web site.