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 4

A Review of the Literature Published During 1979

By G. Pattenden

The Royal Society of Chemistry

Copyright © 1981 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-854-7

Contents

Chapter 1 Saturated and Unsaturated Hydrocarbons By D. C. Horwell, 1,
Chapter 2 Aldehydes and Ketones By S. C. Eyley and D. K. Rainey, 26,
Chapter 3 Carboxylic Acids and Derivatives By D. W. Knight, 87,
Chapter 4 Alcohols, Halogeno-compounds, and Ethers By R. C. F. Jones, 138,
Chapter 5 Amines, Nitriles, and Other Nitrogen-containing 172 Functional Groups By G. Kneen, 172,
Chapter 6 Organometallics in Synthesis Part I The Transition Elements By D. J. Thompson, 196,
Chapter 7 Saturated Carbocyclic Ring Synthesis By A. P. Johnson, 243,
Chapter 8 Saturated Heterocyclic Ring Synthesis By W. J. Ross, 279,
Chapter 9 Strategy and Design in Synthesis By S. Turner, 335,
Author Index, 358,

CHAPTER 1

Saturated and Unsaturated Acyclic Hydrocarbons

BY D. C. HORWELL

1 Saturated Hydrocarbons

Metallocarbenes have been implicated in the iridium-catalysed isomerization of branched hydrocarbons, such as that of 2-methylpentane (1) to 3-methylpentane (3). Studies with 13C-labelled (1) support a mechanism which proceeds via (2) as intermediate. Polymer-bound triphenylphosphine–lithium diorganocuprates may offer advantages in the Wurtz-type coupling of alkyl halides, in that work-up is easier and the product is not contaminated with residual tertiary phosphine. However, yields in general are comparable with those from the corresponding homogeneous reagents.

The air-stable, water soluble ruthenium(n) hydride, [(η6-C6Me6)Ru(µ- H)2 (µ-Cl)Ru(η6-C6Me6)]Cl, is extremely effective in the hydrogenation of double bonds and aromatic systems. Thus styrene is reduced to ethylcyclohexane in quantitative yield at 50°C under 50 atm pressure during 36 h. Cobalt(II) salts and sodium borohydride together appear to be a promising reagent for the selective reduction of olefins. For example, the reagent is able selectively to reduce the terminal double bond of limonene in 79% yield, with no reduction of the trisubstituted double bond.

Di-iododimethylsilane appears to be an effective reagent for the mild deoxygenation of α-arylalkanols to the corresponding hydrocarbon. Aliphatic alcohol methanesulphonates are selectively reduced in good yield by an electrochemical method. The reaction is performed in a divided cell with a lead cathode and a platinum anode in dry DMF containing tetraethylammonium toluene-p-sulphonate. Yields are in the range 57 — 87%, and groups such as esters, olefins, nitriles, and even epoxides are inert under these conditions.

Kabalka and Chandler now report improved yields (83 — 98%) in the deoxygenation reaction of aldehydes and ketones, on treatment of their corresponding tosylhydrazones with catecholborane in the presence of tetrabutylammonium acetate as the base.

2 Olefinic Hydrocarbons

More evidence has appeared showing that the olefin metathesis reaction can tolerate the presence of functional groups. The catalytic system Re2O7- Al2O3, promoted by a small amount of tetramethyltin, effects metathesis of olefins in fair yield (17 — 40%) in the presence of unsaturated ethers and ketones, alkenyl esters, and halogeno-alkenes. The reaction is performed in carbon tetrachloride as solvent at room temperature over 6 h. Electro-reduction of tungsten hexa-chloride with an aluminium anode in halogenated solvents appears to form a complex suitable for a clean metathesis, exemplified by the conversion of pent-2-ene into its equilibrium mixture with but-2-ene and hex-3-ene.

A direct combination of acetylenes and alkanes in a novel pericyclic reaction to generate olefins has been reported. However, yields are low (0.2 — 20%) and vigorous conditions of temperature (350 — 400°C) and pressure (350 — 500 bar) are required (Scheme 1).

Two new procedures which bring about the isomerization of double bonds have been described. The readily synthesized secondary allylic ethers of 2-hydroxy-benzothiazole (4) react with functionalized organocuprates regioselectively in high yield to give the olefins (6). An E : Z ratio of 98:2 may be achieved when the reaction is performed at –78°C; the reaction probably proceeds via an intermediate such as (5) and has been particularly useful in the synthesis of E-monoene alcohol systems found in insect sex attractants, as exemplified in Scheme 2. Allylic acetates and phenyl ethers are readily converted into the corresponding terminal olefin in high yield, on reaction with ammonium formate in the presence of palladium catalysts. Thus geranyl acetate (7) is converted into dihydromyrcene (8) and the corresponding 2-olefin in a ratio of 94:6 in almost quantitative yield. 12

The regio- and stereo-selective alkylation, alkenylation, and arylation of olefins via metallated species continues to attract attention. This methodology enables the direct cross-coupling of olefins to give a wide variety of derivatives. The monoalkyl-olefin (9) may be alkylated in one step to the corresponding 1,1-dialkyl-olefin (10), on reaction with a two-fold molar excess of trialkylaluminium mixed with bis(cyclopentadienyl)titanium dichloride in methylene chloride as solvent. The reaction appears to be sensitive to steric effects, as larger alkylaluminium reagents give low yields. Trialkylboranes may now be transformed into three moles of the corresponding Grignard reagent on treatment with pentane-1,5-bis(magnesium bromide) in toluene. This technique has been applied to the direct stereospecific alkylation of terminal olefins with the so formed Grignard reagents of vinyl halides, in the presence of palladium catalysts (Scheme 3). Murahashi and his co-workers have provided further illustrations of the superiority of palladium-catalysed cross-coupling of alkenyl halides with organo-lithium reagents over other metal catalysts, in terms of yields and stereoselectivity. However, the economic factors should not be overlooked in comparing the use of this expensive metal with the other techniques that are available. Grignard reagents may directly replace the alkoxy-group of enol ethers (11) to give the corresponding alkylated olefins (12), in the presence of bis(triphenylphosphine)nickel chloride. Yields are good and the reaction generally proceeds with retention of configuration.

Alkenylboranes are readily obtained by monohydroboration of acetylenes. Palladium catalysts in the presence of a base, such as sodium ethoxide, effect the coupling of the alkenylboranes with aryl halides to give arylated E-alkenes in good yield. The reaction proceeds with retention of configuration with respect to the alkenylborane. A general procedure for the preparation of the useful E-2-methyl-1-alkenyliodides has been described. These compounds are versatile precursors of trisubstituted olefins. The procedure involves the addition of trimethylaluminium to acetylenes in the presence of organo-zirconium reagents, followed by iodination. E-1-Chloro-1-alkenes and mixed 1,1-dihalogeno-1-alkenes are also readily prepared from 1-chloroacetylenes on reaction with lithium aluminium hydride followed by addition of the appropriate halogen.

Conditions have been described whereby both the alkenyl groups of a homocuprate reagent (13) can be utilized in the formation of Z-dialkylolefins (14). High yields are obtained with both allylic and benzylic halides. α-Halogenoethers similarly give Z-allylic ethers.

Substituted vinylsilanes are useful intermediates in the synthesis of stereo-chemically defined olefins. A new synthesis of substituted vinylsilanes (16) from the silylvinyl Grignard reagent (15) has been achieved. An alternative procedure is by silylation–dehydrosilylation of a trimethylsilylacetylene (17) to give the alkylvinylsilane (18) in 97% overall yield (Scheme 4). Z-1-Chloro- or -bromo-2-trimethylsilylethylenes (20) are readily obtained stereospecifically by halogenation of trans-1,2-bistrimethylsilylethylene (19), involving anti-addition of the halogen, followed by dehydrohalogenation (Scheme 5). More vigorous conditions are needed to produce the corresponding iodo-compound as an equal mixture of both the Z– and E-isomers. Substituted vinylsilanes are now accessible by the nickel-catalysed addition of Grignard reagents to silylacetylenes, although stereoselectivity is not good. However, the procedure does offer a short route to terpenoids, as illustrated by the synthesis of geraniol (Scheme 6).

The trimethylsilylacetylene (21) may serve as a common precursor to both the corresponding E– and Z-trisubstituted series of olefins in good yield and high stereoselectivity (Scheme 7). This procedure is essentially a development of the work of Zweifel and Lewis reported last year.

Helquist and his co-workers have now given more useful experimental details of the stereoselective synthesis of trisubstituted olefins by addition of alkyl-copper complexes, especially methylcopper, to acetylenes (Scheme 8). Clean results are obtained consistently only if the copper(I) bromide-dimethylsulphide complex (22) is white in appearance and its solutions are colourless. If either the solid or solution develops a pink colour (indicative of CuII salts) then larger amounts of dienes formed from coupling of the alkenyl-copper intermediates (23), are obtained. Complex (22) is best stored under nitrogen, although manipulation is performed routinely in air with no noticeable change in appearance. The techniques allow stoicheiometric amounts or only a small excess of the copper reagent to be used. However, long reaction times (~120 h) are necessary for the best results.

The cis conjugate addition of the organocopper–organoborane complex (R1Cu.BR23) to α,β-acetylenic carbonyl compounds occurs smoothly at –70 to –20°C. Stereospecificity to give E-alkyl-olefins is highest when the corresponding terminal acetylenes are used as the substrate. Chromium(II)–amine complexes (e.g. ethylenediamine, triethylamine) reduce alkylphenylacetylenes to produce Z-olefins with high stereoselectivity (Scheme 9). Terminal olefins are also reduced, but internal dialkylacetylenes are not reactive towards this reagent.

The substitution of allylic sulphones by Grignard reagents has been shown to be catalysed by 1% [Cu(acac)2] to give a one-step route to either the α- or the γ-coupled products. 29 Primary allylic sulphones favour the γ-product, whereas secondary allylic sulphones give a mixture of both α- and γ-products.

Several papers have appeared dealing with the synthesis of strained bridgehead olefins (anti-Bredt olefins). Conditions are described whereby a 10:1 mixture of the olefins (25) and (26) is formed by the vacuum pyrolysis of the bridgehead chloro-compound (24). The olefin (25) can form a reversible stabilized complex with [Pt0(PPh3)2], and this same catalyst can also effect irreversible isomerization to (27).32 The lead tetra-acetate-induced oxidative decarboxylation of the propellane carboxylic acid (28) produces the stable olefin (29) in good yield.

An intramolecular Wittig reaction has given the first optically active anti-Bredt olefin (30) with known absolute configuration. The diolefin (31) is thermally labile, and isomerizes to (32) with a half-life of 314 min at 25°C. The interesting bridgehead olefins (33) and (34) have not been isolated, but have been characterized as their Diels–Alder adducts, or dimers, respectively.

Reich has now described the ready preparation of α-lithio-selenides and -selenoxides, which smoothly condense with aldehydes and ketones. The resultant β-hydroxy-selenides and -selenoxides can be reductively eliminated under very mild conditions to give tetrasubstituted olefins, which are not readily available from the Wittig reaction. The β-hydroxyselenides can be converted into olefins under milder conditions than their sulphur equivalents, using methanesulphonyl chloride in triethylamine.

Quaternization of selenides with methanesulphonyl fluoride or methyl iodide–silver tetraftuoroborate, followed by elimination with potassium t-butoxide in THF or DMSO at room temperature, offers an alternative procedure to selenoxide elimination. An advantage appears to be the formation of the volatile side product dimethyl selenide, rather than the selenenic, seleninic, or selenoic acids produced in selenoxide fragmentations, which may react with other functionality present in the molecule. Krief and his co-workers now report that β-hydroxysulphides are reductively eliminated to give di- and tri-substituted olefins on reaction with P2I4 or PI3, or to tetrasubstituted olefins on treatment with SOCl. β-Hydroxysulphoximines also undergo reductive elimination with sodium amalgam to yield olefins. The corresponding β-hydroxy-sulphides, -sulphoxides, and -sulphones do not eliminate under comparable conditions. Marshall reports further details of the reductive elimination of cyclic vic-cyanohydrins by a syn-elimination with sodium naphthalenide (NaC10H8) in HMPA. anti-Elimination may also take place when lithium in ammonia is used as the base. Sodium in liquid ammonia has been found to be a suitable base for the reversal of selenolactonization to form the corresponding olefin in good yield. This may be a useful complement to the iodolactonization protection–deprotection sequence for sensitive olefin substrates such as prostaglandins. Fluoride ion, derived from Bun4NF.3H2O, appears to be an excellent base for the elimination of 11-silyl-sulphones to give terminal olefins [e.g. (36) and (37) in Scheme 10]. Primary alcohols are dehydrated on alumina in better yield than by pyrolysis of the corresponding xanthate esters, although some double-bond isomerization may occur.

Further elimination procedures that are mild enough for use in carbohydrate chemistry have been developed. Samuelsson and Garegg have found that the triphenylphosphine–tri-iodoimidazole complex converts vic-diols into olefins in hexopyranoside systems in high yield [e.g. (38)->(39)]. Photolysis of the ortho-iodobiphenyl ether of the galactopyranose (40) has given the exo-methylene compound (41) in good yield. The product is contaminated with a little of the corresponding unsubstituted biphenyl ether (42).

The elimination of hydrogen halide to give olefins occurs in high yield where potassium t-butoxide is used as the base in the presence of 18-crown-6. Conditions have been reported whereby vic-dihalides can give either vinyl halides, on treatment with solid sodium hydroxide in glyme, or acetylenes on reaction with solid potassium hydroxides in glyme or tetraglyme. A peculiar reaction involving the syn-elimination of fluoride ion from (43) to give the vinyl bromide (44) appears to be restricted to where the ‘complex base’ sodamide-sodium t-butoxide is used. Other bases give the expected dehydrobrominated product.

The threo-3-hydroxycarboxylic acids (45) are readily obtained in high diastereoisomeric purity on condensation of dilithio-salts of carboxylic acids with aldehydes. Further purification is achieved on recrystallization from chloroform. The pure condensate (45) may serve as a common precursor to both E– and Z-olefins or enol ethers (Scheme 11). Treatment of (45) with the Ph3P–EtCO2N=NCO2Et complex gives the zwitterion (46), which undergoes anti-elimination to give the Z-olefin (47). Alternatively, if (45) is activated as its benzenesulphonyl ester, the β-lactone (48) is formed which undergoes syn-elimination of carbon dioxide to give the E-olefin (49). In general, yields are good in both cases, with stereochemical purity of the olefin products greater than 97%.

The Wittig reaction has been extended to convert both aromatic and aliphatic esters directly into the corresponding isopropenyl compounds (50) on reaction with methylenetriphenylphosphorane. The reaction does not appear to work for α-stabilized phosphoranes. Scheme 12 summarizes other variations on the conversion of carbonyl groups into terminal olefins described this year. The transformation of 1-alkyltosylprop-2-ones (51) into the 2-tosyl-1-alkenes (52) involves a novel addition–elimination sequence which proceeds in good yield.

(Continues…)Excerpted from General and Synthetic Methods Volume 4 by G. Pattenden. Copyright © 1981 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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