A series of reviews by leading specialists in their fields which gives systematic and comprehensive coverage of the progress in major areas of research.

General and Synthetic Methods Volume 15

A Review of the Literature Published in 1990

By G. Pattenden

The Royal Society of Chemistry

Copyright © 1993 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-974-2

Contents

Chapter 1 Saturated and Unsaturated Hydrocarbons By A.R. Howell and S.P. Keeling, 1,
Chapter 2 Aldehydes and Ketones By L.P. Crawford and S.K. Richardson, 32,
Chapter 3 Alcohols, Halogeno Compounds, and Ethers By J.B. Sweeney, 75,
Chapter 4 Amines, Nitriles, and Other Nitrogen-containing Functional Groups By G.M. Robertson, 127,
Chapter 5 Organometallics in Synthesis By S.E. Thomas, M. Wills, and E. Merifield, 175,
Chapter 6 Saturated Carbocyclic Ring Synthesis By J.D. Kilburn, 262,
Chapter 7 Saturated Heterocyclic Ring Synthesis By S.D.A. Street and J. Steele, 301,
Chapter 8 Highlights in Total Synthesis of Natural Products By C.E. Mowbray, G. Pattenden, and M. Tankard, 356,
Chapter 9 Reviews on General and Synthetic Methods Compiled by S.M. Higton und G. Pattenden, 419,
Author Index, 428,

CHAPTER 1

Saturated and Unsaturated Hydrocarbons

BY A.R. HOWELL AND S.P. KEELING

1 Saturated Hydrocarbons

New approaches to effect deoxygenations of alcohols and their derivatives, as well as improvements on existing protocols, have been disclosed. Thus, β-cyclodextrin promotes the hydrogenolysis of allylic alcohols to olefins using hydrogen and hydridopentacyanocobalt, which is generated in situ. The principal products are trans-internal olefins, but tertiary allylic alcohols and those possessing a trisubstituted double bond do not react. Allylic alcohols, as well as saturated and benzylic alcohols, can be deoxygenated with the tungsten (II) complex, WCl2(PMePh2)4. Reaction rates vary widely (<1min. – 3 weeks), and double bond migration is sometimes observed. Thiols are also reduced by the complex. Electron rich benzylic alcohols can be reduced to the corresponding hydrocarbons with sodium borohydride trifluoroacetic acid (TFA). It is crucial for good yields that the TFA is added slowly to a mixture of the substrate and sodium borohydride in tetrahydrofuran. Benzylic alcohols can also be deoxygenated by radical-induced reactions with lithium aluminium hydride. tris(Trimethylsilyl)silane, diphenylsilane, and triethylsilane have been reported as comparable, or superior, alternatives to tributyltin hydride in the Barton-McCombie reaction. In an interesting extension of Barton’s observation of varying rates of Bu3SnH induced reduction between particular thiocarbonate ester derivatives of primary and secondary alcohols, Sekine and Nakanishi have shown that 3′,5′-dioxynucleosides can be converted into their 3′-deoxy derivatives by selective reduction of the corresponding bis-phenoxythiocarbonyl derivative (1) (Scheme 1). Benzylic and allylic alcohols can be hydrogenolysed as their acrylate or cinnamate derivatives by the action of triethylsilane in the presence of Wilkinson’s catalyst.

Chloro-, bromo- and iodoaromatic compounds are dehalogenated reductively in the presence of KOH/polyethylene glycol (400) in boiling xylene. Alkyl bromides and iodides, as well as alkyl isocyanides, selenides and xanthates, can be reduced in good to excellent yields with either tris(methylthio)silane or tris(isopropylthio)silane. A combination of a catalytic quantity of iodide and phosphorus acid in refluxing acetonitrile has been shown to dehalogenate a variety of 2-chloro- and 2-bromocarbonyl compounds in moderate to excellent yields (74-87%). α-Bromoketones can also be dehalogenated cleanly by the chemoselective action of di-n-butyltin clihydride.

Water soluble alkenes are converted in high yields into alkanes upon treatment with palladium (II) acetate and triethoxysilane. Alkynes can be selectively transformed into either alkanes or alkenes (predominantly Z), depending on the number of equivalents of silane. Selective platinum-catalysed hydrogenations of olefins in the presence of terminal alkynes are possible when the alkyne is silyl-protected. The selectivity seems to be largely based on steric effects, since alkyne reduction does occur once terminal olefin reductions are complete, and disubstituted olefins require bulkier silyl groups on the alkyne moiety. β-Cyclodextrin and polyethylene glycol (400) are useful phase-transfer agents for the hydridopentacyanocobaltate anion-catalysed hydrogenation of conjugated dienes to monoolefins. The apparent regioselectivity of this cerium or lanthanide promoted reaction varies with the substitution pattern on the diene.

Two potentially useful reductive deoxygenations of ketones have been disclosed. In one procedure, a tandem denitration-deoxygenation of α-nitroketones is effected in good to excellent yields via lithium aluminium hydride reduction of the corresponding (p-tolylsulfonyl)hydrazone derivatives. Although perhaps not widely applicable, the useful conversion of acyl N-protected pyrroles to alkyl pyrroles is accomplished using a borane-tert-butylamine complex in the presence of aluminium chloride.

Alkyl iodides undergo coupling reactions with the nickelacycle (2) in the presence of anhydrous manganese (II) iodide, resulting in the formation of β-substituted propionic acids in good yields (Scheme 2). Another interesting coupling process involves the homo-coupling of alkyl halides, in the presence of an activated form of zerovalent copper. Allyl and benzyl halides and, also, primary alkyl iodides undergo homocoupling in high yields. However, secondary and tertiary iodides and bromides give only moderate to low yields, where eliminations and reductive dehalogenations predominate. Cyclisations of α,ω-dihaloalkanes have also been found to be feasible. Moderate to high yields result for smaller rings (3 membered rings best) with substantially reduced yields with increasing chain lengths.

2 Olefinic Hydrocarbons

Three new approaches to the cis-selective semihydrogenation of alkynes have been reported. Thus, terminal alkynes are reduced at room temperature by the stable, readily prepared copper (I) hydride reagent, [(Ph3P)CuH]6; elevated temperatures are required for unactivated, internal alkynes. Regio- as well as stereospecific cis-reductions of a wide variety of acetylenic derivatives can be achieved in absolute ethanol with zinc powder activated with 1,2-dibromoethane or zinc powder treated with dibromoethane, followed by lithium bromocuprate. Greater selectivity is realised under the first set of conditions, and both methods have the advantage over poisoned palladium catalysts of experimental simplicity, as well as shortened reaction times. Low-valent Group V metal reagents, prepared from NbCl5 or TaCl5 and zinc in a mixed solvent system of dimethoxyethane (or THF) and benzene, also yield Z-alkenes from alkynes.

Olefins undergo smooth bond migration to their thermodynamically more stable form on treatment with easily prepared potassium fluoride impregnated alumina. In the examples cited, terminal alkenes were isomerised to internal alkenes, and exocyclic double bonds to endocyclic ones.

An interesting communication has shown that 1-phenylethanols dehydrate more efficiently in the solid state than in solution. The reactions proceed at room temperature in excellent yield (≥ 97%) in the presence of either gaseous HCl (reaction conducted in a dessicator) or Cl3CCO2H, the latter giving complete conversion in less than 5 minutes.

Schwartz and Meier have further explored vanadium (V)-induced decarboxylations/eliminations of 3-hydroxy carboxylic acids. Trichloro(p-tolylirnino)vanadium (V) (3) was found to be superior to VOCl3 and can be utilised in making tetrasubstituted olefins (Scheme 3).

Vicinal diols can be converted into olefins by a novel reagent system consisting of chlorodiphenylphosphine, imidazole and iodine in an inert solvent. 1,2-Diols, functionalised as their cyclic sulfates, can also be transformed into alkenes by reaction with sodium naphthalenide. In examples where E or Z-isomers are possible, the thermodynamically preferred alkene predominates. Reactive metallocenes, prepared by reaction of Cp2MCl2(M=Ti, Zr, Nb) with one equivalent of magnesium, reduce oxiranes to alkenes very efficiently. When M=Ti or Zr, some geometric isomerisation occurs. α,β-Epoxy silanes undergo synchronous insertion of an alkyl group and deoxygenation when treated with organolithium or organolanthanoid reagents. E-α,β-Epoxy silanes are transformed into desilylated, alkylated E-olefins, whilst the Z-isomers give Z-vinylsilanes (Scheme 4).

The reductive debromination of vicinal dibromides to olefins can be achieved by reaction with bis(triphenylstannyl)telluride coupled with fluoride ion or with catalytic sodium selenite. It has been observed that vicinally disubstituted compounds bearing a pair (not necessarily matched) of radical leaving groups, such as chloro-, bromo-, phenoxy thiocarbonyloxy or imidazolylthiocarbonyloxy, can be converted in high yields (60-90%) into the corresponding alkenes by reaction with Bu3SnH and AIBN.

The transformation of primary amines into alkenes can be accomplished by a sequence consisting of their conversion to N-nitrosoamides, followed by rhodium-catalysed thermal rearrangement. This overall process constitutes a mild, nonbasic alternative to the classical Hofmann elimination.

2,2′-Bipyridine-modified nickel complex reducing agents have been shown to desulfurise vinyl thioethers, sulfoxides and sulfones in a chemoselective manner, leaving the double bond intact. Although the yields are reasonable, the stereoselectivities are variable.

The carbonyl group is a widely exploited precursor of olefins, and improvements on established procedures, as well as novel approaches to this transformation, have been revealed. In two reports Schlosser et al. have disclosed that tris(2-methoxymethoxyphenyl)phosphine-derived ylids give excellent (≈ 200:1) cis-selectivities with unbranched, saturated aldehydes. Z-Alkenes of the stilbene type are accessible if tris(2-ethoxymethoxyphenyl)phosphonio(phenylmethanide) (4) is allowed to react with aromatic aldehydes. Davis and Chen have found that N-sulfonyloxaziridines (5) and, also, (6) can be employed for the oxidation of alkylidenephosphoranes to alkenes in very good yields (63-99%) and high E-stereoselectivities (Scheme 5). A new version of the Peterson olefination employs bis(trimethylsilyl)methyl derivatives with fluoride ion as a catalyst to generate the required α-silylcarbanion. Although the yields are very good, the stereoselectivities are quite variable. Imidazolyl sulfones have been proposed as alternatives to phenyl sulfones in Julia olefinations, because the reductive elimination of the product β-hydroxy imidazolyl sulfones can be readily effected with SmI2. Again, good yields are realised, but with only moderate stereoselectivities. It has been demonstrated that dimethyltitanocene (Cp2TiMe2), which is a relatively stable compound prepared from methyllithium and titanocene dichloride, is an attractive alternative to the Tebbe and Grubbs reagents for the methylenation of aldehydes, ketones, esters or lactones. Silylated sulfonyl-hydrazones, such as (7), undergo nucleophilic attack, followed by sigmatropic rearrangement, as shown in Scheme 6, leading to alkenes. It is worthy of note that the method is equally effective for reactions between a saturated aldehyde sulfonyl derivative and a vinyl anion. Olah and Wu have disclosed that polycyclic ketones can be converted into olefins by a two step sequence which first involves epoxide formation with trimethylsulfoxonium ylid. The epoxide is then treated with a dialkylcuprate, followed by thionyl chloride (Scheme 7). Another approach to neopentylidenation is offered by the same authors and involves dibromomethylenation of the ketones, followed by treatment with t-butyllithium (Scheme 8).

Palladium catalysed cross-coupling reactions continue to play an important role in stereodefined alkene construction. Thus, in a modification of standard conditions, allylic acetates, usually unreactive in cross-coupling with tin reagents, will react with arylstannanes with the use of DMF as solvent in the presence of 3 equiv. of LiCl, 3 mol% Pd(dba)2 and in the absence of added phosphine, leading to alkenes (Scheme 9). The ally! acetate undergoes regioselective coupling at the primary allylic carbon, rather than at secondary and tertiary centres. Dienes are readily accessible when vinylstannanes are used instead of aryltin reagents. In these cases, the double bond geometry of the vinyltin partner is retained. In another procedure aryl or 1-alkenyl triflates undergo stereospecific, palladium-catalysed coupling reactions in the presence of potassium phosphate with alkyl-, aryl- or 1-alkenylboron compounds in high yields under mild conditions (Scheme 10). The triflates fall somewhere between bromides and chlorides in reactivity as electrophiles in their coupling with organoboron compounds. In a novel one-pot reaction, trans-stilbenes are isolated from a substitution/cross-coupling protocol promoted by an interlamellar montmorillonite palladium catalyst (Scheme 11).

Brown and Rangaishenvi have demonstrated that α-haloallylboronate esters are useful intermediates in transfer reactions with organolithium and Grignard reagents, leading to α-alkyl or α-aryl substituted allylboronate esters (8), as shown in Scheme 12. The boronate esters (8) can then be readily transformed into three-carbon homologated alkenes by heat-induced boratropic rearrangement, followed by protonolysis (Scheme 12).

Geminal dichlorides undergo reductive dimerisations to symmetrical E-olefins in the presence of iron (II) oxalate in refluxing anhydrous dimethylformamide. The reactions are quick (40-90min) and efficient (84-92% isolated yields).

3 Stereoselective, Simultaneous Formation of sp3 and sp2 Centres

Claisen Rearrangement. – Yamamoto et al. have reported further on the utility of bulky organoaluminium reagents in the promotion of stereoselective Claisen reactions. Confirming preliminary accounts, the aluminium compounds (9) and (10) have been shown to catalyse the rearrangement of a wide variety of allyl vinyl ethers to alkenones with good to excellent Z– and E– stereoselectivities, respectively (Scheme 13). Furthermore, with chiral starting materials, such as (11), the chirality is conserved in the isolated products (Scheme 14). Attempts to use the chiral organoaluminium reagents (12) and (13) to induce asymmetry in the rearrangement of racemic substrates were not promising (e.e. ~13%). However, when the vinyl moiety was substituted with silyl or germanyl groups e.e.’s up to 93% were realised (Scheme 15). In a further development with the organoaluminium reagent (9), it was shown to provide preferentially the para-isomer with simple allyl phenyl ethers (Scheme 16), a result not observed with either thermal conditions or with conventional Lewis acids. Another efficient promoter of the Claisen rearrangement of allyl phenyl ethers is Montmorillonite clay, producing chiefly ortho-substituted allyl phenols. The allyl group transfers selectively in a [1,3]-fashion when it has two terminal substituents.

2- Allyloxyethyl aryl sulfoxides (14) are efficient precursors of allyl vinyl ethers. The sulfoxides, which are readily prepared from the Michael addition of alcohols (even tertiary ones) to phenyl vinyl sulfoxides, undergo facile thermal reorganisation in decalin without an added Lewis-acid promoter (Scheme 17).

4 Conjugated and Non-conjugated Dienes

Lithium diisopropylamide in the presence of catalytic quantities of potassium tert-butoxide (LIDAKOR) smoothly converts homoallylic ethers into conjugated dienes (Scheme 18). Where possible, the new double bond is formed with high trans-selectivity, while the configuration of the existing double bond is unchanged. Allylic ethers treated with LIDAKOR undergo regio- and stereoselective 1,4-elimination (Scheme 18). Regioisomeric ratios can vary as a function of the base concentration. Acyclic bis-secondary 2-ene-1,4-diols undergo transformation into 1,3-dienes in the presence of iodotrimethylsilane. The reaction is largely nonstereospecific for simple acyclic cases; however, l,4-diaryl-2-butene-1,4-diols are converted into E,E-butadienes.

3-Sulfolenes (15) are frequently used as stable precursors to substituted butadienes. However, their applicability as synthons of 2-alkylated and 2,3-dialkylated butadienes has been largely unexplored. It has now been disclosed that 3-(phenylsulfonyl)-3-sulfolenes (16) can be alkylated in good yields at the 3-position upon treatment with n-butyllithium in THF at -105°C in the presence of HMPA (4 equiv.) (Scheme 19).

(Continues…)Excerpted from General and Synthetic Methods Volume 15 by G. Pattenden. Copyright © 1993 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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