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 3

A Review of the Literature Published During 1978

By G. Pattenden

The Royal Society of Chemistry

Copyright © 1980 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-730-4

Contents

Chapter 1 Saturated and Unsaturated Acyclic Hydrocarbons By D. C. Harwell, 1,
Chapter 2 Aldehydes and Ketones By S. M. Roberts, 36,
Chapter 3 Carboxylic Acids and Derivatives By D. W. Knight, 75,
Chapter 4 Alcohols, Halogeno-compounds, and Ethers By R. C. F. Jones, 132,
Chapter 5 Amines, Nitriles, and Other Nitrogen-containing Functional Groups By G. Kneen, 164,
Chapter 6 Organometallics in Synthesis Part I The Transition Elements By D. J. Thompson, 183,
Chapter 7 Saturated Carbocyclic Ring Synthesis By K. Cooper, M. Mellor, and G. Pattenden, 227,
Chapter 8 Saturated Heterocyclic Ring Synthesis By W. J. Ross, 265,
Chapter 9 Strategy and Design in Synthesis By S. J. Turner, 312,
Chapter 10 Photochemistry in Synthesis By A. B. Holmes, 329,
Author Index, 365,

CHAPTER 1

Saturated and Unsaturated Acyclic Hydrocarbons

BY D. C. HORWELL

1 Introduction

Volume 1 of the much heralded treatise ‘Comprehensive Organic Chemistry’ has now appeared, and has three chapters devoted to saturated hydrocarbons, olefinic hydrocarbons, dienes, polyenes, and acetylenic hydrocarbons. Two reviews summarize olefin synthesis via β-functionalized organosilicon compounds, with discussion of stereochemical control vis à vis the Wittig reaction. Clive has surveyed modern organoselenium chemistry, including the conversion of epoxides into olefins, inversion of olefinic geometry, selenoxide fragmentation, and the conversion of β-hydroxyalkyl selenides into allylic alcohols and olefins. Selective reactions with diethylaluminium–2,2,6,6-tetramethylpiperidine, including stereo- and regio-selective isomerizations of substituted epoxides into allylic alcohols and their further regiospecific transformation into 1,3-dienes, are discussed. Warren has reviewed the use of migrating Ph2PO and PhS groups in the synthesis of 1,3-dienes and allylic alcohols and modern routes to interesting sterically crowded olefins are summarized by Tidwell. Selective eliminations on alumina surfaces to give olefins are reviewed by Posner, whilst Oppolzer and Snieckus have discussed the use of the intramolecular ‘ene’ reaction in organic synthesis. A detailed review on the use of alkenyl-, alkynyl-, and cyanoborates as synthetic intermediates to alkynes, diynes, and enynes, and their stereochemical control of di-, tri- and tetra-substituted olefin synthesis, has appeared. Olefin photochemistry is analysed in terms of the rearrangements and fragmentations that may occur, and some such reactions are illustrated by the industrial synthesis of Vitamin D. Stang has reviewed the generation of unsaturated carbenes and their addition to other unsaturated moieties to give cumulenes and acetylenes. Further chemistry of poly-unsaturated hydrocarbons is included in a review on the synthesis of the chiral component of insect pheromones, and applications of the retro-Diels–Alder reaction in organic synthesis have been summarized.

2 Saturated Hydrocarbons

Alternative procedures to catalytic hydrogenation for the reduction of olefins to alkanes have appeared this year. A particularly smooth procedure has been the utilization of sodium hydrogen telluride as illustrated in Scheme 1. Ashby and co-workers have studied the reduction of olefins with bis-d1-iso-propylaminoalane, and with magnesium hydride, both catalysed with [Cp2TiCl2]. Lithium aluminium hydride-transition-metal mixtures also reduce olefins and halides, with catalytic amounts of CoCl2 and NiCl2 particularly effective. Itaconic acid is hydrogenated asymmetrically in 83.5% (S) optical yield by benzoyl (2S, 4S)-4-diphenylphosphino-2-diphenylphosphinomethyl-pyrrolidine, and hydrogen transfer with cyclohexene-Pd-C-A1Cl3 has been shown to be effective in hydrogenating both aryl olefins and aryl alcohols to aylalkanes.

Selective reductive removal of functional groups as a synthetic route to alkanes has been further developed this year. Two research groups report new mild procedures for the reduction of esters and sterically hindered alcohols to the corresponding alkanes in good yield, and without any rearrangement. Thus, tertiary steroidal acetates are reduced by Li–EtNH2 or K–ButNH2–18- crown- 6, and methane sulphonate esters by lithium triethylborohydride (Scheme 2). Sodium in HMPA is also an effective new reagent for both the reduction of esters and the deoxygenation of alcohols to give alkanes. Deoxygenation of ketones and primary alcohols may be achieved under mild conditions in good to excellent yield, by reduction of their phenylselenoacetals and selenides respectively, with triphenyltin hydride; the selenoacetals are readily prepared from the aldehyde or ketone using the easily available crystalline reagent tris(phenylseleno)borane, in the presence of TFA. In addition to this procedure, aldehydes and ketones are deoxygenated directly in good yield with triethylsilane in the presence of gaseous boron trifluoride, and thioketones are readily desulphurized by four equivalents of [HFe(CO)4]-. Kornblum and his co-workers have described a highly efficient method for the replacement of a nitro-group by hydrogen, on treatment with the sodium salt of methyl mercaptan in an aprotic dipolar solvent at room temperature. The reduction probably proceeds via a radical anion process, and can tolerate the presence of other functionality, such as the cyano-, keto-, and ester groups (Scheme 3).

The photocatalytic decarboxylation of saturated carboxylic acids to alkanes has been shown to occur on TiO2 powder. The direct replacement of primary aliphatic amino-groups for hydrogen, termed ‘hydrodeamination’, takes place readily under mild conditions, on treatment with hydroxylamine-O-sulphonic acid and sodium hydroxide;33 the reaction works well even on amino-acid and dipeptide substrates. Aliphatic amines may also be used to introduce the triftuoromethyl group directly, by the novel procedure outlined in Scheme 4.

3 Olefinic Hydrocarbons

Several factors which influence the rate and yield of the ‘ene’ reaction have been identified this year. Gladysz and Yu have found that the thermal ene reaction of β-pinene, which otherwise occurs only at temperatures greater than 150 °C, proceeds readily at room temperature under 40 kbar pressure (39 500 atm). For example, methyl pyruvate and β-pinene have been reported to react at 165 °C to afford the adduct (1) in 55% yield. Since (1) undergoes a rapid retro-ene reaction at this temperature, this yield is believed to represent the maximum equilibrium yield attainable. However, (1) is formed in quantitative yield at room temperature at 40 kbar pressure!

The intramolecular ene reaction of the 1,6-enyne (2) appears to be retarded by a terminal methyl substituent, but significantly accelerated by an electron-withdrawing substituent, such as the methoxycarbonyl group. These observations are pertinent to the conversion (2) -> (3) in a synthetic strategy to the iridoid carbon skeleton.

The eutectic mixture AlCl3–NaCl–KCl has been found to be a superior catalyst to A1Cl3 alone, in the Lewis acid-catalysed ene reaction of methyl acrylate with terminal olefins. Hence an 86 : 14 mixture of geometrical isomers of (4) is obtained from octene; the ester (4) is a useful intermediate in the synthesis of the sex pheromone from the Douglas Fir Tussock moth, and of its biologically active isomer.

The olefinic ketone (5) is the major component (52% ) in a mixture of four products from an apparent ene reaction of an allylic cation with isobutylene; the cation is formed by treatment of an α,α’-dibromo-ketone with iron carbonyl.

An extensive literature has appeared this year devoted to the stereospecific and stereoselective construction of di-, tri-, and tetra-substituted double bonds. This has been largely due to advances in methodology in the use of organometallic agents as a response to the stereochemical and homologation problems encountered in the synthesis of biologically important isoprenoids, such as farnesol, squalene, and the juvenile hormones. Corey has now extended the Harvard programme for computer-assisted synthetic analysis (LHASA) to include suggested antithetical schemes to olefin target molecules. Several strategies for stereoselective olefin and polyene synthesis, which have been implemented in several test cases, are described.

In four papers Trost gives f urther details of the scope and limitations of the formation of π-allylpalladium complexes and their application to stereochemical ‘allylic alkylation’ with soft nucleophiles. The use of these complexes in prenylation is demonstrated in a short stereoselective route to all-trans-farnesol from methyl geranoate. The ‘allylic alkylations’ attainable are outlined in Scheme 5. Further studies on the reaction of π-allylpalladium complexes with carbanions are reported by Hegedus and co-workers.

The direct coupling of two unlike alkenyl groups, for example via vinylic cuprates and vinyl iodides, has not proved useful as a stereospecific process. However, Dang and Linstrumelle have now shown that stereospecific substitution (>97% ) of alkenyl iodides with a variety of Grignard reagents can occur in high yield and under mild conditions, when catalysed with tetrakis(tri-phenylphosphine)palladium (Scheme 6). Linstrumelle and his co-workers have also extended the regioselective alkylation procedure of the Grignard reagent (6), reported last year, to reactions with epoxides. The ‘normal’ γ-products (7) are mainly formed when no catalyst is present, but the abnormal α-products (8) are formed predominantly in the presence of 10% copper(I) iodide (Scheme 7). In contrast, the prenyl-lithium, generated from dimethylalkyltriphenyltin, gives the γ-product in good yield and isomeric purity, but in the ptesence of 10% copper(r) iodide little regiospecificity is indicated in a product mixture containing 55% γ- and 45% α-products. The new alkylating agent C+uR BF3-, prepared in situ from an alkyl-lithium, copper(I) iodide, and boron trifluoride etherate, shows exclusive γ-alkylation in reactions with alkyl halides.

Murahashi et al. reported last year that allylic alcohols undergo direct α-substitution with copper(I) iodide and alkyl-lithium reagents in the presence of N,N-methylphenylaminotriphenylphosphonium iodide. The same group of workers have now shown that the corresponding tributylphosphonium iodide directs the substitution preferentially to the γ-position, as illustrated in Scheme 8.

The stereochemically controlled addition of organometallic species of copper, tin, silicon, palladium, zirconium, and boron to acetylenes has been investigated as a route to di-, tri-, and tetra-substituted olefins. The carbon–metal bond thus formed is cleaved in a stereoselective manner either directly, or indirectly, via the corresponding vinyl-lithium reagents with a wide variety of electrophiles. In three papers Negishi and his co-workers show how cis-addition of Me3Al–Cl2ZrCp2 to terminal acetylenes provides a general route to trisubstituted olefins (9), with >98% stereoselectivity. The scheme has been readily adapted to a one-step synthesis of geraniol (10) and ethyl geranoate, from 6-methylhept-5-en-1-yne (Scheme 9). Where difficulty has been encountered with palladium- or nickel-catalysed cross-coupling of alkenylaluminium, or zirconium compounds with alkenyl, aryl, or alkynyl halides, then catalytic amounts of zinc chloride can significantly increase the yield of the cross-coupled product.

Helquist and his co-workers finds that the dimethyl sulphide-copper(I) bromide complex with methylmagnesium bromide will add to simple terminal acetylenes in stoicheiometric amounts, or in only a small excess (10 — 15%); this procedure allows a more efficient means of constructing stereochemically defined methyl trisubstituted olefins found in natural isoprenoids (Scheme 10).

Confirmation that cis-addition of alkyl copper complexes occurs in these reactions has been obtained by studies of lanthanide-induced shift 1H n.m.r. spectra of the products. Corey has now introduced (3-methyl-3-methoxybut-1-ynyl)copper in THF as a relatively inexpensive reagent for the generation of mixed cuprates (Oilman’s reagents), which enable coupling reactions to occur in high yield with alkyl-lithium reagents.

Trialkylboranes may also be used to convert terminal acetylenes into trisubstituted olefins stereospecifically, via the vinyl-lithium reagent generated by Normant’s procedure (Scheme 11). The stereochemistry of the product is of opposite configuration to that prepared earlier by Evans and his co-workers via the corresponding boronate esters. Alkenyldialkylboranes (11), derived from internal acetylenes, give the corresponding Z-olefin (12) in good yield on treatment with catalytic amounts of palladium diacetate at room temperature. This result is in sharp contrast to the palladium diacetatetriethylamine decomposition of alkenylboranes, derived from terminal acetylenes, which give rise to the corresponding E-olefins.

The mono-addition of cuprates to benzenesulphonylacetylene leads to a mixture of E- and Z-adducts (13), the relative amount of each isomer being dependent on the steric bulk of the R-group in the cuprate.

Vinyl silanes continue to attract attention as intermediates for the stereoselective synthesis of olefins. Zweifel and Lewis now describe the stereoselective synthesis of both E-and Z-(1-halogenoalk-1-enyl)silanes (15) from alk-1-ynyl-silanes, and show how they may then be processed to dialkyl-substituted vinyl-silanes, alkenyl halides, and trisubstituted olefins (Scheme 12). The E-1-halogenoalkenyltrimethylsilanes are readily prepared in high isomeric purity by treatment of the dialkylhydroalumination adduct (14) with N-chlorosuccinimide, bromine, or iodine; the corresponding chloro- and bromo-Z-isomers are obtained by the isomerization of the E-isomers. In addition to these findings, Snider has reported that nickel(acac)2-trimethylaluminium catalyses Grignard additions to alk-1-ynylsilanes producing a mixture of vinyl organometallic compounds (16). These adducts are very reactive towards a wide range of electrophiles (Scheme 13). Thus, addition of the mixture of isomers (16) to excess iodine gives a 9 : 1 mixture of the vinyl iodide (17) in 71% yield, and the separated isomers serve as precursors to tri- and tetra-substituted olefins as indicated in Scheme 12. Treatment of (16) with vinyl bromide gives an 85 : 15 mixture of the 1,3-diene (18) in 48% yield, along with 15% of the corresponding dimer. Regioselective cis-hydroboration of 1-trimethylsilylalk-1-ynes similarly generates vinylboranes, which produce the corresponding α-trimethylsilylvinyl-lithium reagents on treatment with methyl-lithium. These also can be converted into trisubstituted vinylsilanes, with retention of stereochemistry.

Chan and his co-workers have condensed α-trimethylsilyl-lithium with carbonyl compounds to give trisubstituted vinyl silanes, but the stereoselectivity is dependent on the relative sizes of the substituents on the carbonyl group. Disubstituted vinyl silanes, derived from terminal acetylenes, serve as useful precursors for the stereoselective preparation of vinyl halides.

Vinyl stannanes, derived from terminal acetylenes and tri-n-butylstannane, are readily cleaved by butyl-lithium to give vinyl-lithium reagents; the latter are useful precursors to vinyl halides and they also undergo conjugate addition with cycloalkenones; the latter property has found use in a route to prostaglandins.

Ashby and his co-workers have reported that the reagents MgH2–CuI and MgH2–CuOBut reduce both internal and terminal acetylenes stereoselectively to the corresponding cis-olefins, with no trans-impurities or over-reduction to the alkanes. These new reagents, once prepared, may be superior to catalytic hydrogenation, in terms of the purity of the product and convenience of pro- cedure.

The addition of the reagent [Cp2Zr(H)Cl] to terminal acetylenes occurs stereospecifically, leading to a vinyl zirconium complex, which in the presence of catalytic amounts of anhydrous [Ni(acac)2] undergoes rapid conjugate addition to α, β-unsaturated ketones (Scheme 14).

(Continues…)Excerpted from General and Synthetic Methods Volume 3 by G. Pattenden. Copyright © 1980 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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