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 16

A Review of the Literature Published Between January 1991 and July 1992

By G. Pattenden

The Royal Society of Chemistry

Copyright © 1994 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-834-9

Contents

Chapter 1 Saturated and Unsaturated Hydrocarbons By R.P.C. Cousins, 1,
Chapter 2 Aldehydes and Ketones By L.P. Crawford and S.K. Richardson, 37,
Chapter 3 Carboxylic Acids and Derivatives By T. Harrison, 92,
Chapter 4 Alcohols, Halogeno Compounds, and Ethers By J.B. Sweeney, 195,
Chapter 5 Amines, Nitriles, and Other Nitrogen-containing Functional Groups By G.M. Robertson, 250,
Chapter 6 Organometallics in Synthesis By C.F. Marcos, S. Ferrio, O. Riant, S.E. Thomas, and M. Wills, 292,
Chapter 7 Saturated Carbocyclic Ring Synthesis By J.D. Kilburn, 402,
Chapter 8 Saturated Heterocyclic Ring Synthesis By S.D.A. Street and J. Steele, 450,
Chapter 9 Highlights in the Total Synthesis of Natural Products By D.C. Harrowven, M.J. Kiefel, and G. Pattenden, 506,
Chapter 10 Reviews on General and Synthetic Methods Compiled by G. Pattenden, 562,
Author Index, 568,

CHAPTER 1

Saturated and Unsaturated Hydrocarbons

BY R.P.C. COUSINS

1 Saturated Hydrocarbons

The development of radical deoxygenation procedures for derivatives of alcohols, using tin and silicon hydrides, has continued. The elimination of tin-based reagents has been seen as an objective in this work, because of the associated toxicity and environmental hazards. Triethylsilane in the presence of benzoyl peroxide is a satisfactory alternative which deoxygenates suitably functionalised primary and secondary alcohols in high yields. Dimethyl or diethyl phosphite has also been used to replace tributyl tin hydride, but also requires benzoyl peroxide as an initiator.

The ability of tris(trimethylsilyl)silane to reduce a range of organic halides, selenides, xanthates and isocyanides to the corresponding hydrocarbons has been highlighted, whilst similar reductions using dimethyl phosphite have also been published. The electroreductions of organic halides to hydrocarbons in the presence of a catalytic amount of SmCl3 proceed in good yields.

Catalytic hydrogenations of unfunctionalised olefins using chiral organolanthanide complexes have been shown to proceed with enantiomeric excesses of up to 96%; however, organoyttrium complexes enable catalytic hydrogenations of terminal olefins in the presence of substituted double bonds (Scheme 1). Sodium or lithium hydrogen selenide has been used for the selective reduction of the olefinic linkage of α,β-unsaturated carbonyl compounds in the presence of a terminal double bond (Scheme 2).

A zirconium-catalysed ethylmagnesation reaction with alkenes has enabled regiocontrolled double alkylation or hydroxyalkylation to be achieved in good yield. (Scheme 3).

The trapping of a carbon radical generated during a radical-based decarboxylative procedure with vinylphenylsulphone leads to an adduct (1), which can then be reduced to give the homologue (2) or alkylated before reduction to afford the hydrocarbon derivative (3) has been described (Scheme 4).

Tertiary, secondary, and benzylic alcohols can be alkylated reductively using trialkylboron and trifluoromethanesulphonic acid.

2 Olefinic Hydrocarbons

Dixanthantes of vic-diols can be easily deoxygenated to the corresponding olefins using triethylsilane and benzoyl peroxide in a radical reaction, both in cyclic and acyclic systems. This transformation can also be accomplished with diphenylsilane and AIBN. The sulphone adduct (1) produced during a radical decarboxylation, was smoothly converted via the vinyl sulphone (4) with sodium telluride into the corresponding terminal olefin; the procedure constitutes an overall methylenation of the acid (Scheme 4).

Dicyclopentadienyldimethyltitanium, a reportedly more stable version of the Tebbe reagent, allows direct methylenation of aldonolactones in good yields. Comparison of the Tebbe and Wittig reagents for ketone methylenation has indicated better product yields with the Tebbe reagent, particularly when using hindered ketone substrates. It has also been noted that the non-basic medium of the Tebbe reagents prevents racemisation of sensitive chiral centres. Benzylidenations of carbonyl compounds using dibenzyltitanocene leading to moderate stereoselectivities have been reported (Scheme 5).

The zinc-zirconium heterobimetallic reagents (5), which can be prepared readily by hydrozirconation of alkenylzinc halides, react with aldehydes to produce E-disubstituted olefins with high stereoselectivity whereas ketones lead to a mixture of stereoisomers (Scheme 6). Cyclic α-iodoenones and triflyloxyenones react smoothly with alkenylzinc derivatives in the presence of a catalytic amount of a palladium-phosphine complex to afford α-alkenylenones. Conjugate reduction of the adducts then leads to the corresponding α-alkenyl ketones with retention of stereochemistry (Scheme 7). The 1,2-metallate rearrangement of lithiodihydrofuran and dihydropyran systems using Grignard reagents in place of organolithium reagents has been accomplished with copper (I) catalysis leading to γ- and δ-alkenols respectively with high stereoselectivity (Scheme 8). A tandem ring opening-elimination reaction of erythro– or threo-secondary tetrahydrofurfurylic acetates with TMSCl/NaI affords pure Z– or E-γ-iodoalkenes, respectively (Scheme 9).

A one-step, palladium-promoted intermolecular coupling reaction involving three different alkenes and enabling a quick entry into the prostaglandins from the readily available chiral alcohol (6) has now been extended to a number of analogues (Scheme 10).

Indium trialkyls have been used in cross coupling reactions with chloroalkenes and allylic chlorides to afford alkylated systems in good yields. It was noted in these studies that all three alkyl groups in the indium reagent were transferred, rather than one group as in the case of aluminium trialkyls; however, only moderate stereocontrol was achieved. Tetraorganoindates, which are prepared by the addition of organolithium reagents to trialkylindium, have been shown to react with allyl bromides in the α-position with retention of stereochemistry at room temperature.

A simple method for dehydrating tertiary alcohols to the corresponding thermodynamically most stable alkene has been described which uses boron trifluoride etherate in methylene chloride at 25°C (Scheme 11).

The stereocontrolled reduction of mono- and disubstituted alkenyl halides with tributyltin hydride in the presence of a catalytic amount of a Pd(O) complex has been developed and the method works efficiently for iodides at 25°C, but for bromides a temperature of 75°C was required (Scheme 12). The reductions of monosubstituted allyl chlorides using DIBAL, in the presence of a Pd(O) catalyst, are complete at low temperatures without competitive isomerisation (Scheme 13). The conversion of vicinal dibromides to alkenes can be achieved using aluminium foil in the presence of catalytic dicyclopentadienyltitanium chloride in high yield at room temperature.

Epoxides are deoxygenated to the corresponding alkenes through the use of a complex prepared from VCl3(THF)3 and zinc; however, the reaction with acyclic cis-epoxides was shown to proceed with partial inversion of configuration. The trans-α-epoxystannanes (7) are alkylated reductively with excess alkyllithium reagents to afford the corresponding trans-alkenes (Scheme 14).

Partial reductions of alkynes via a niobium or a tantalum complex, generated from NbCl5-Zn or TaCl5-Zn, have been shown to give the Z-alkene selectivity upon treatment with sodium hydroxide (Scheme 15). Similarly, alkynes can be reduced selectively to cis-olefins under mild conditions using SmI2 mixed with a first row transition metal catalyst and a proton donor. The stereoselection was reversed to give trans-alkenes by the addition of HMPA. Rieke zinc has also been found to effect the conversion of alkynes to Z-alkenes with high stereoselectivity.

Hydrozirconation of terminal acetylenes, followed by transmetallation of the resulting vinyl zirconates with a higher order cyanocuprate, afford mixed vinylic cuprates which undergo alkylation with epoxides, activated halides and vinyl and primary triflates to give trans-1,2-disubstituted olefins in a one-pot procedure (Scheme 16).

Further developments of the Peterson olefination reaction have allowed the facile conversion of α-hydroxysilanes to α-lithio silanes (8); generation of the latter species has been problematic. Addition of the freshly generated silane (8) to aldehydes followed by elimination affords disubstituted alkenes. Conversion of the α-iodosilane (9) to the corresponding α-silylketone (10) allows Cram controlled addition of various nucleophiles and thus provides a triply convergent method for the production of predominantly one β-hydroxy silane isomer. Subsequent treatment with acid or base then leads to the E– or Z-alkene, respectively (Scheme 17). An alternative approach to α-silylcarbanions via α-stannyl-silanes has also been reported. Additions of these reagents to aldehydes, and subsequent elimination, leads to olefinic products with modest stereocontrol (Scheme 18). The Peterson methylenation procedure has been modified to include a simple filtration of an acid resin used in the elimination of the intermediate β-hydroxy silanes to give olefinic products in good yield (Scheme 19).

A stereocontrolled conversion of ketones into Z-olefins via S-(β-oxoalkyl)thiophosphates (11)or Se-(β-oxoalkyl)selenophosphates (12) has been reported to proceed in good yields (Scheme 20).

Direct replacement of the sulphonyl group of a primary or secondary alkylsulphone with a methylene or alkylidene chain has been accomplished with modest stereocontrol by treatment of α-sulphonyl carbanions with chloromethyl- or iodomethyl-magnesium chloride or 1-chloropentyl-magnesium chloride solutions (Scheme 21).

Hydroborations of aldehyde-derived enamines by 9-borabicyclo[3.3.l]nonane (9-BBN), followed by methanolysis afford terminal alkenes in good yields. Cyclic and heterocyclic ketone-derived enamines have also been utilised in this procedure to afford disubstituted olefins, whilst the same acyclic ketonic enarnine substrate can be converted into the required Z– or E-alkene by modification of the hydroboration-elirnination procedure (Scheme 22).

3 Stereoselective, Simultaneous Formation of sp3 and sp2 Centres

Claisen Rearrangements. – Conversion of allylic alcohols, derived from the coupling of an aldehyde with a vinyl organometallic reagent, to the corresponding allylic xanthate has allowed a [3,3]-sigmatropic rearrangement to provide dithiocarbonates; subsequent radical reduction then leads to E-alkenes as the major product (Scheme 23). The asymmetric Claisen rearrangement of cis-allylic α-(trimethylsilyl)vinyl ethers (13) catalysed by the chiral organoalurninium reagent (14) affords acylsilanes (15) which possess the same absolute configuration as those derived from the corresponding trans-allylic ether. A boat-like transition state (16) has been proposed rather than the normal chair-like transition state (17) in view of the possible severe 1,3-diaxial interactions in (17) (Scheme 24). The stereocontrol in ester enolate Claisen rearrangements has been investigated, and a novel stereoelectronic effect in pyranoid and furanoid glycal systems was found to enable significant relative stabilisation of the boat-like against the chair-like transition state. The preferred transition state in 6- and 5-membered carbocyclic systems was found to be highly dependent on steric factors due to the small energy differences between the boat- and chair-like transtion states. In contrast, in straight chain substrates the chair-like transition state was the most important except in very specialised systems (Scheme 25). Claisen rearrangements to chiral R– and S-3-acyloxy-E– vinyl silanes have given access to a wide range of α-chiral-β-silyl-E-hexenoic acids in good diastereoselectivities from simple propionate esters, and by using chelation or non-chelation control conditions selectivities for syn:anti glycolate esters of 23:1 and 1:36 were obtained respectively (Scheme 26). Good diastereoselectivities were observed in the ester enolate Claisen rearrangement of allyl α-fluoroacetates leading to 2-fluoroalkenoic acids despite reported difficulties of stereoselective deprotonation of fluoroacetates.

Studies on the carbanion accelerated Claisen rearrangement using the phosphine oxide, phosphonate and phosphonamide carbanion stablising groups have been described. The N,N’-dibenzyl-1,3,2-diazaphospholidine group was found to be optimal in the preparation of substrates and ease and stereoselectivity of rearrangement (Scheme 27). Application of the Claisen rearrangement to a series of tertiary allylic sulphone esters provides trisubstituted double bonds stereoselectively and in good yield (Scheme 28). Treatment of allene carbamates (18) with trialkyl ortho esters in the presence of acid affords alkyldienoates in modest yields (Scheme 29).

A thio-Claisen rearrangement has been shown to proceed at room temperature with good stereocontrol leading to α-allyl-β-hydroxy-γ-methyl dithioesters (Scheme 30).

High diastereoselectivities were observed through the use of boron enolates in an Ireland-Claisen rearrangement of 0-protected 2-butenyl glycolates where higher rates of rearrangement compared to silyl ketene acetals or lithium enolates were observed; however, poor enantioselectivities (0-10% e.e) were obtained with chiral reagents (Scheme 31). The use of the chiral boron reagent (19) has allowed the first enantioselective Ireland-Claisen rearrangement with achiral esters to proceed in high selectivity leading to either erythro or threo product after the selective generation of the Z– or E-enolate, respectively (Scheme 32).

[2.3] Wittig Rearrangements. – Treatment of 4-hydroxyphenyl 3′-substituted allyl ethers in refluxing aqueous methanol with KOH and oxygen has been shown to produce products consistent with a tandem [2,3]-Wittig, Cope rearrangement. In contrast the lack of 3′-substitution in the starting material enabled base-catalysed Claisen rearrangement (Scheme 33). Application of these sequential rearrangements to allyl propargyl ethers (20) first with a [2,3]-Wittig rearrangement and then after selective reduction an anionic oxy-Cope process allowed preparation of either threo or erythro aldehyde products with good selectivity. This procedure was applied to optically pure substrate to furnish a key intermediate in the synthesis of (+)-faranal, a trail pheromone of the Pharaoh’s ant, without loss of stereointegrity (Scheme 34).

Nitrogen substituted β-methallyldimethylammonium ylides containing an electron withdrawing group in the α-position, and those with a vinyl group and a β-ester moiety undergo stereoselective rearrangement to E– or Z-trisubstituted olefins at low temperatures in the presence of potassium t-butoxide (Scheme 35). Treatment of silylketene acetals of α-allyloxy esters with Lewis acids induces a [2,3]-Wittig shift to afford 2-hydroxy-4-alkenoic acids with high erythro-selectivity. The use of (-)-8-phenyl menthyl derivatives leads to poor asymmetric induction suggesting random trans-metallation from both faces of the silyl ketene acetal (Scheme 36).

The [2,3]-Wittig rearrangement of tertiary allyl ethers derived from (+)-camphor and (-)-fenchone has been shown to lead to two olefinic products in an E:Z ratio of 7:3, and single Z-olefin product respectively. Good asymmetric induction was observed, and the chiral auxiliary was cleaved subsequently using ozone (Scheme 37).

4 Conjugated Dienes

The direct metallation of isoprene with sterically hindered potassium dialkylamides followed by reaction with a range of electrophiles gives the expected coupling products in reasonable yields (Scheme 38). A facile conversion of allylic alcohols into conjugated dienes in good yields has been reported, possibly via a syn elimination pathway, using phosphorus oxychloride and pyridine at room temperature.

(Continues…)Excerpted from General and Synthetic Methods Volume 16 by G. Pattenden. Copyright © 1994 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.