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 11

A Review of the Literature Published in 1986

By G. Pattenden

The Royal Society of Chemistry

Copyright © 1989 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-924-7

Contents

Chapter 1 Saturated and Unsaturated Hydrocarbons By By N. Simpkins, 1,
Chapter 2 Aldehydes and Ketones By K.E.B. Parkes, 43,
Chapter 3 Carboxylic Acids and Derivatives By D.W. Knight, 89,
Chapter 4 Alcohols, Halogeno-compounds, and Ethers By L.M. Harwood, 208,
Chapter 5 Amines, Nitriles, and Other Nitrogen-containing Functional Groups By C.M. Marson, 262,
Chapter 6 Organometallics in Synthesis By S.E. Thomas and T. Gallagher, 393,
Chapter 7 Saturated Carbocyclic Ring Synthesis By T.V. Lee, 518,
Chapter 8 Saturated Heterocyclic Ring Synthesis By K. Cooper and P.J. Whittle, 547,
Chapter 9 Highlights in Total Synthesis of Natural Products By K. Carr, D.J. Coveney, and G. Pattenden, 612,
Reviews on General and Synthetic Methods Compiled by K. Carr, D.J. Coveney, and G. Pattenden, 659,
Author Index, 668,

CHAPTER 1

Saturated and Unsaturated Hydrocarbons

BY N. SIMPKINS

1 Saturated Hydrocarbons

A new radical method for the deoxygenation of secondary alchols has appeared. The method consists of first reacting the alcohol with 2,2′-dibenzothiazolydisulphide in the presence of Bu 3P leading to the corresponding sulphide derivative (1), which is then reacted with Bu3SnH to give the hydrocarbon product in excel lent yield (Scheme 1).

A wide variety of aryl aldehydes and ketones can be deoxygenated by a mixture of ZnI2 and NaCNBH3 in dichloroethane. The reagent also gives good results with benzylic, allylic and tertiary alcohols, although attempted reduction of α,β-unsaturated ketones gave complex mixtures of products. Highly efficient conjugate reduction of α,β-unsaturated ketones and aldehydes is possible by use of a three component system comprising a palladium catalyst, a hydrosilane, and zinc chloride (Scheme 2). The same task of conjugate reduction can be accomplished on unsaturated esters, usually in near quantitative yield, using magnesium in methanol.

2 Olefinic Hydrocarbons

The protonolysis of alkenyldialkylboranes to give Z-alkenes can be conducted, in most cases, under neutral conditions-using methanol. More hindered alkenyldisiamylboranes react less well, unless a small amount of a carboxylic acid is added. A variety of Z-alkenyl pheromones was prepared using this method. The synthesis of trans-alkenes and unsymmetrical ketones was also accomplished using vinylic organoborane chemistry.

Cross-coupling reactions are now possible between aryl (or vinyl) halides and trialkylboranes by the use of catalytic palladium (Scheme 3). The reaction appears not to suffer from side reactions due to β-hydride elimination which are normally observed in such processes. The reduction of allylic acetates to the corresponding alkenes has been reported using SmI2 with a Pd(0) catalyst. The reaction gave high yields of deoxygenated products; unfortunately, mixtures of regioisomers usually result.

Brandsma has illustrated the use of a new and highly potent basic mixture comprising ButOK, BuLi and TMEDA, by efficient generation of vinylpotassium from ethene.

Warren’s examination of the Horner-Wittig reaction continues with two more papers detailing the stereoselective reduction of α-R2PO – ketones. The phosphorane (2) is normally rather unreactive: however addition of NaH produces the ylide anion (3) which reacts with aldehydes to give predominantly Z-products (Scheme 4).

The homologation of esters via a DIBAL reduction and phosphonate extension sequence is a commonly desired transformation. The DIBAL reduction to give an aldehyde suitable for homologation is often plagued by over-reaction problems, so that a reduction-reoxidation procedure is often required. These problems can be overcome by the neat trick of carrying out the ester reduction in the presence of the phosphonate anion. The Seyferth-Wittig reagent often gives vinylated by-products (4), as well as the usually desired allylsilanes (5) (Scheme 5). Efficient and stereoselective formation of the syn-vinylated product (4) can be promoted by choice of suitable groups on silicon. Wittig-type olefination reactions can be carried out using tungsten alkylidene complexes, and by the use of in situ generated chloromethyl lithium (Scheme 6).

Diiodo alkenes have been prepared via a Wittig-like reaction which requires no base. Me3SiCl accelerates the reaction of both catalytic and stoichiometric copper reagents with unsaturated carbonyl compounds to give the desired silylenol ethers.

An extensive study of the Co2(Co)8-catalysed reaction of acetates and lactones with CO and HSiEt2Me has appeared. This reaction constitutes a very general, mild and high-yielding synthesis of siloxymethylidene products (Scheme 7).

Vinyl sulphides are available by reaction of phenylthiocarbenes with nitrile anions. Yields on the whole are fair to good, and with some modification several intramolecular versions are possible (Scheme 8). Vinyl sulphides, vinyl selenides and ketene seleno(thio) acetals are formed in high yield by reaction of an appropriate vinyl bromide or dibromide with PhSe- or PhS- in the presence of a Ni(II) catalyst. β-Phenylthio-nitro-olefins have been prepared as mixtures of stereoisomers as shown in Scheme 9.

Oxidation of the sulphide (6) to either the corresponding sulphoxide or sulphone was also possible, and the products were used in Diels-Alder reactions.

Alkenyl fluorides are available by reaction of the corresponding lithio compound with N-tert-butyl-N-fluoro-benzene sulphonamide (Scheme 10).

Two new reports extend the chemistry of fluorinated vinyl organometal lics. In the first, trifluorovinyl l ithium is shown to be much more stable in Et2O (up to -30°C) than in THF. Remarkably, the other research paper by the same group reports that the corresponding zinc reagent F2C=CF-ZnCl is stable for several days in THF at room temperature. These findings allowed considerable extension to the synthetic repertoire of these reagents. A variety of fluorinated products, including perfluoroalkylated alkenyl iodides are available via a pal ladium-catalysed reaction between perfluoroakyl iodides (RfI) and alkynes. This method and two other routes to alkenyl iodides are outlined in Scheme 11. The use of bis(pyridine)iodotetrafluoroborate (7) in conjunction with various metal salts gave good yields of the desired 1,2-iodofunctionalised olefins. Curran’s notable contributions to radical chemistry continue with a novel reaction which isomerises hex-5-ynyl iodides to the product (iodomethylene)cyclo-pentanes.

2,2-Disubstituted vinylsilanes have been prepared in regio and stereoselective fashion by reaction of aryl iodides with alkynyl silanes in the presence of a pal ladium catalyst. This and another pal ladium-catalysed transformation leading to aryl vinysilanes are outlined in Scheme 12. The latter process, involving arylation of trimethylvinylsilane with aryl iodides takes place smoothly if silver sal ts are included in the mixture; otherwise styrenes are formed via a presumed addition-desilylpal ladation. The scope of the palladium mediated addition of silylstannanes to acetylenes highlighted last year has been further examined. Allenes react with bis(phenyldimethylsilyl)cuprate to give either vinylsilanes or al lylsilanes depending on the structure of the al lene (Scheme 13). The intermediate allyl or vinyl copper reagents could also be reacted efficiently with other electrophiles such as MeI, CH3COCl, etc. The addition of PhMe2SiBEt3Li or Bu3SnBEt3Li to acetylenes occurs cleanly using CuCN as catalyst (Scheme 14). This stereospecific cis-addition also exhibits good regioselectivity, especially if CoCl2(PPh3)2 is employed in place of CuCN, in which case the terminal isomer (8) is the exclusive product. A related report from the same research group describes another synthesis of vinyl silanes by reacting alkenyl halides with (R3Si)3MnMgMe. Two other notable entries to vinyl silanes have appeared and examples are shown in Scheme 15. The first sequence uses the known stereoselective boron to carbon migration of an alkyl group using Me3SnCl as the electrophilic trap. The boron group is then selectively attacked using n-BuLi, CuBr-SMe2 to give the alkenyl copper which can then be coupled with either al ly! bromide or methyl iodide. In the other method enol triflates are coupled with distannanes in a similar fashion to the well-established reaction with organostannanes.

A number of (1-cyclohexenyl)diphenylphosphine oxides were prepared by Diels-Alder reaction of 2-(diphenylphosphinyl)-1,3-butadiene with suitable partners.

Allylically unsaturated cyclic ethers of the same general type have been prepared by the research groups of Overman and Trost. Thus suitably substituted vinyl silanes undergo Lewis acid mediated intramolecular attack on a methoxyethoxymethyl (MEM) ether to give cyclic products, e.g. (9) (Scheme 16). The preparation of (10) by use of the trimethylenemethane (TMM) reagent (11) (which will not normally react with carbonyl groups) was made possible by the addition of Bu 3snOAc in catalytic quantities.

Allylic alcohols (12) are formed when α,β-epoxy sulphides are treated with 3-5 equivalents of BuLi at -70°C (Scheme 17). Interestingly, clean desulphurisation to give the epoxide product (13) was also possible by the use of less BuLi at -100°C.

Opening of vinylic epoxides by organomercurials, mediated by palladium also gives allylic alcohols, as do two other new methods which use epoxides as starting materials (Scheme 18). Thus transformation of chloromethyl epoxides to 2-substituted allylic alcohols occurs on exposure to telluride ion. Methylmagnesium-N-cyclohexylisopylamide is a new, mild reagent for isomerisation of epoxides.

The scope of the synthesis of allylic amines and their protected derivatives via sigmatropic rearrangement of selenilimines (14) hasen examined (Scheme 19). The reaction works well unless very sterically conjested products are being formed, and has some advantages over the original Sharpless procedure which provided the products as sulphonamides. Al lylic amines have also been prepared via pal ladium catalysed azidation of allylic acetates, and by an elegant nitrone route described by DeShong (Scheme 20). Thus, reaction of nitrones with vinyl silanes followed by reduction provides Peterson – type intermediates which can then be eliminated to either Z- or E-products. Homoallylic amines were also prepared using al lylsilane in the initial cycloaddition. Substitution reactions of allylic nitro compounds have received considerable attention and some examples are outlined in Scheme 21. In each case, examination of the regiochemistry of the reaction was of paramount concern, the results using palladium being superior to the Sncl4 mediated process. Allylic sulphides constitute yet another group of products accessible by palladium mediated al lylation. Excellent yields of al lylstannanes are obtained in a new ultrasound-promoted preparation, (Scheme 22). The method is highly attractive in its simplicity, and gives isomerical ly pure compounds in some cases. Fleming has described further work on the synthesis of allylsilanes. Thus stereoselective aldol condensation of a β-silylenolate, e.g. (15), with an aldehyde was fol lowed by a decarboxylative elimination to provide the allylsilane stereoselectively (Scheme 23). The corresponding trans-allylsilane could also be prepared from (16) using an alternative elimination via the β-lactone. Stereocomplementary sequences were also possible using the Z-enolate corresponding to (15).

A survey of transition metal catalysts, and ligands identified [Ir-(COD)(PPh3)2] PF6 as the most efficient for the isomerisation of alkenyl silanes to allylsilanes (Scheme 24). By-products of the reaction include vinyl silane and saturated silanes.

A new electrochemical oxidative cleavage of allylsilanes and benzylsilanes produces allyl or benzyl ethers.

Asymmetric modifications of the palladium-catalysed al lylic alky lation reaction have appeared from several laboratories. Very good results were obtained in the reaction of racemic allylic acetates with soft carbon nucleophiles in the presence of optically active ferrocenylphosphine ligands (Scheme 25). The products could be obtained in up to ca. 90% ee and in high yield. Kinetic resolution of racemic allylic acetates was also found to be possible. A similar asymmetric process combines an allyl acetate with a prochiral nucleophile to give the chiral al lylated product (Scheme 26). Using the Schiff base (17) derived from glycine, the allylated amino ester (18) was prepared in up to 57% ee. Asymmetric preparations of homoal lylic alcohols have also appeared, most notably by reaction of allylic tin complexes with aldehydes.

Metallic zinc or iron in the presence of Bicl3 can be used to mediate the reaction between allylic halides and aldehydes to give homoallylic alcohols. The method displays notable chemoselectivity betweeen aldehydes and ketones, and alcohol or phenol groups can be incorporated in the substrates without protection. Both Roush and Brown have publ ished studies of the stereoselective synthesis of homoallylic alcohols using various allylboron reagents (Scheme 27). Thus Brown made use of Z- or E-crotyl diisopinocamphenylborones, e.g. (19) prepared in situ, to give any of the four possible isomeric β-methyl homoal lyl alcohol products in excel lent de and ee. Scheme 27 also highlights Roush’s results using tartrate-modified crotylboronates such as (20) with chiral aldehydes. A number of cyclic homoal lyl alcohols were obtained using radical cyclisation of vinyl radicals onto trimethylsilylenol ethers (Scheme 28).

The problem of stereoselective construction of exocyclic alkenes has been addressed by two methods, both. starting with alkynes. Thus stereoselective al lylmetallation of propargyl alcohols yielded intermediates capable of further elaboration by zirconium – promoted bicyclisation – carbonylation (Scheme 29). The other approach used the stereospecific conversion of an alkynyl trialkylborate to a trisubstituted olefin, via the migration of an alkyl group from boron to carbon.

3 Conjugated 1,3-Dienes

Hydrodimerisation of terminal alkynes to give symmetrical trans, trans – 1,3-dienes can be carried out straightforwardly by use of a CoCl2/NaBH4/PPh3 system: internal alkynes are unaffected. A wide variety of conjugated dienyl products are available by employing the palladium – catalysed coupling of alkenyl boronates with various aryl ,vinyl or al lyl halides (Scheme 30). Both mono- and disubstituted alkenyl boronates can be employed in this sequence, thus allowing for a high degree of flexibility. The same group of research workers has also published some closely related work enabling stereoselective synthesis of (Z,Z)-1-bromo-1,3-dienes.

Various dienyl alcohols and lactones were amongst the products prepared by reaction of allylic acetates with carbonyl compounds (Scheme 31). The method suffers from a lack of selectivity, both stereo – and regio-isomers being formed in most cases. A variety of 1-nitro-1,3-dienes were prepared by treatment of the corresponding dienes with trifluoroacetyl nitrate (prepared in situ), followed by an elimination step using KOAc (Scheme 32).9 The dienyl products are sensitive to both acid and base but can be purified by distil lation or by flash chromatography on silica gel impregnated with sodium carbonate. A new short route to dienyl-tin products proceeds via hydrozirconation of conjugated enynes, followed by transmetallation using Bu3SnCl.

Vinyl triflates can be coupled efficiently to various organotin compounds. Further details of this chemistry have now appeared including efficient preparations of trimethylsilyldienes (Scheme 33). Two other routes to silyldienes are outlined in Scheme 34. Reduction of allenic alcohols (21) gave moderate yields of the dienyl products, although the stereoselectivity of the process leaves much to be desired. The second method, involving hydroboration of the allene (22) is much more stereoselective and enables either isomer of the final product to be obtained depending on the elimination conditions used. A key application for such dienes is in Diels-Alder reactions, where the products have vinylsilane functionality for further modification. This type of chemistry has now been explored with 2,3-bis (trimethylsilyl)buta-1, 3-diene, itself readily available by dimerisation of organolithium (23) (Scheme 35). Diels-Alder chemistry of the silyl-substituted diene (24) and of 2-tributylstannyl-1,3-butadiene (25), has also been reported (Scheme 36). Reaction of (24) with a suitable dienophile gives an intermediate, e.g. (26) which, after elimination, undergoes a second cycloaddition. The scope of the sequence is quite broad, enabling heterocycloadditions and (3+4) cycloadditions to be incorporated. The vinylstannanes resulting from cycloadditions with (25) are rather versatile, as was demonstrated by conversion to an α,β-unsaturated acid.

(Continues…)Excerpted from General and Synthetic Methods Volume 11 by G. Pattenden. Copyright © 1989 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.