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 13

A Review of the Literature Published in 1988

By G. Pattenden

The Royal Society of Chemistry

Copyright © 1992 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-944-5

Contents

Chapter 1 Saturated and Unsaturated Hydrocarbons By A.R. Howell, 1,
Chapter 2 Aldehydes and Ketones By K.E.B. Parkes, 33,
Chapter 3 Carboxylic Acids and Derivatives By D.W. Knight, 79,
Chapter 4 Alcohols, Halogeno-compounds, and Ethers By J.B. Sweeney and J. Virden, 156,
Chapter 5 Amines, Nitriles, and Other Nitrogen-containing Functional Groups By G.M. Robertson, 195,
Chapter 6 Organometallics in Synthesis By C.J. Richards, S.E. Thomas, and M. Wills, 250,
Chapter 7 Saturated Carbocyclic Ring Synthesis By J.D. Kilburn, 343,
Chapter 8 Saturated Heterocyclic Ring Synthesis By S.D.A. Street and P.J. Whittle, 372,
Chapter 9 Highlights in Total Synthesis of Natural Products By C.W. Ellwood, D.C. Harrowven, and G. Pattenden, 430,
Reviews on General and Synthetic Methods Compiled by S.M. Higton and G. Pattenden, 461,
Author Index, 469,

CHAPTER 1

Saturated and Unsaturated Hydrocarbons

BY A.R. HOWELL

1 Saturated Hydrocarbons

A variety of new methods for the deoxygenation of alcohols has appeared. Thus, treatment of diaryl methanols with a mixture of dichloromethylsilane and sodium iodide in either acetonitrile or a mixture of dichloromethane and acetone produces diarylmethanes rapidly and in high yields. In addition, diaryl or aryl alkyl carbinols are deoxygenated selectively in the presence of other reducible functional groups (such as hydroxyl or ester) by the action of boron trifluoride etherate and triethylsilane. Tertiary alcohols can be converted into the corresponding alkanes by a two step sequence involving heating a toluene solution of the alcohol with washed Raney nickel, which leads to an alkene/alkane mixture, followed by hydrogenation. Several functional groups, e.g. ethoxylethyl ethers, epoxides, and olefins, do not tolerate the reaction conditions.

Radical deoxygenations of secondary alcohols can be accomplished by the reaction of their dithiocarbonate derivatives with n-Bu3SnH-Et3B. The chemoselective reductive cleavage of allylic acetates of 1,2- and 2,3-unsaturated monosaccharides has been realised by a three component reducing system comprised of diphenylsilane, a soluble palladium(0) catalyst and catalytic amounts of zinc chloride. Hydride substitution proceeds with absolute inversion of configuration (Scheme 1).

Tris(trimethylsilyl)silane reduces alkyl and benzyl chlorides, bromides and iodides in a most effective manner. The method rivals tributyltin hydride in efficiency and is a superior reagent from ecological and practical perspectives. Reductive deselenisation can be performed rapidly, conveniently and in high yield with nickel boride, which is generated in situ by adding sodium borohydride to a tetrahydrofuran solution of nickel chloride hexahydrate.

Selective hydrogenations of carbon-carbon double bonds can be achieved by the simultaneous addition of the substrate alkene and trimethylsilyl chloride or water to Nickel Complex Reducing Agents (NiCRA). The less substituted double bond is preferentially reduced in dienes, and carbonyl, ester or acid moieties are untouched.

An interesting extension of the stereoselective reductions produced by Bakers yeast has been reported. Thus, (E)-2-methyl- and (E)-3-methyl-2,4-pentadien-1-ols are reduced to (S)-2-methyl- and (S)-3-methyl-4-penten-1-ols, respectively, which are useful precursors to bifunctional and enantiomerically pure C6-building blocks, as illustrated in Scheme 2.

2 Olefinic Hydrocarbons

Alkenes are produced in high yield from primary and secondary alcohols by their reaction with 1,1,1-trichloro-3,3,3-trifluoroacetone and a catalytic amount of para-toluenesulphonic acid. Dehydration of 2-octanol gives exclusively trans 2-octene.

Epoxides are converted cleanly to olefins by the action of magnesium reduced titanocene dichloride. trans-Epoxides lead exclusively to trans-alkenes, while cis-epoxides furnish predominantly cis-alkenes. The reduction of epoxides with concomitant alkylation has been accomplished by reaction with lithium tetraalkylcerate. Styrene oxide gives, chiefly, terminal olefins, while alkyl substituted ethylene oxide predominantly affords internal olefins (Scheme 3).

Olefins can be prepared from vicinal dibromides, using sodium O,O-diethylphosphite in the presence of catalytic tellurium. Unlike other reponed tellurium promoted debrominations, this method proceeds at room temperature. The reaction takes place with high anti-stereoselectivity.

Beckmann fragmentation, rather than simple rearrangement, has been observed for ketoximes having α-substitutents (Y) which can stabilise intermediary carbocations (Scheme 4). The control of the stereo- and regiochemistry of the resulting double bond has been difficult. For cyclic ketoximes a solution utilising silicon-directed Beckmann fragmentation has been reported. With a trimethylsilyl group on the β-carbon of the ketoxime, complete regio- and stereoselective double bond formation can be realised, as illustrated in Scheme 5. The methodology has been employed in the synthesis of pheromones.

The much studied Wittig reaction continues to receive attention. In an extension of studies on the semistabilised allylic phosphorus ylides, Tamura et al. have looked at the scope and limitations of these ylides. It was shown that sterically crowded β,γ-disubstituted allylic tributylphosphorus ylides afford E-olefins with high stereoselectivity (>92%). As the steric demand of the ylides decreased, bulky aldehydes were required for E-selectivity. Z-Selectivity resulted when allylic triphenylphosphorus ylides and tertiary aldehydes were employed. Benzylphosphonium ylides, which are also semi-stabilised, produce largely E-olefins upon reaction with aldehydes.

Optically active phosphonates have been utilised to improve the stereoselectivity of exocyclic double bond formation in prostacyclin analogues. The (-)-8-phenyl-menthyl phosphonoacetate (1a) improves the ratio of products (2) and (3) from 1:1 (no chiral auxiliary) to 86:14. The enantiomeric phosphonate (1b) gives the same products in an inverse ratio (15:85) (Scheme 6).

The Wittig-Horner reaction can be used to prepare α-labelled functional olefins (%D>95%). This is accomplished by running the reaction in the presence of a 6M K2CO3-deuterium oxide solution.

The electrolysis of a-substituted phosphonates on Pt or glassy carbon cathodes proceeds with cleavage of the activated C-H bond. The resulting carbanion then reacts further with carbonyl compounds to give olefins in a satisfactory yield.

A new method for carbon-carbon double bond formation, promoted by tri-n-butylphosphine and zinc powder, has been reported. Heating an equivalent amount of an aldehyde, bromoacetic ester, tri-n-butylphosphine and zinc powder (or a catalytic amount) at ~100°C results in exclusive formation of E-olefins in good yield. The procedure is much simpler than the associated Wittig reaction and requires no base or solvent.

Cohen has disclosed an improved, “one-pot” procedure for the preparation of alkylidene- and allylidenecyclopropanes from α-lithio(cyclopropyl)silanes (Scheme 7). The allylidene cyclopropanes (R3=vinyl) have been converted to 2-vinylcyclobutanones by MCPBA oxidation, followed by rearrangement (Scheme 8).

The conversion of olefins to ketones using geminal dialuminoalkane reagents has been investigated. The compounds, CH2(AlClMe)2 and CH2(AlClEt)2, are effective methylenating reagents. Multicarbon aluminium reagents ‘alkylenate’ aromatic ketones in reasonable yields, but aliphatic ketones give a variety of products.

Metal catalysed cross coupling reactions continue to play a dominant role in stereoselective alkene construction. Thus, the cross coupling reaction between organozinc chlorides and (Z)-2-bromo-1-alkenylboranes, prepared by bromoboration of 1-alkynes, in the presence of a palladium catalyst produces 2,2-disubstituted alkenylboranes, which can be transformed directly into di- or trisubstituted alkenes (Scheme 9).

Another palladium catalysed coupling reaction involves vinylic halides or triflates and 3-butenoic or 4-pentenoic acid. The resulting γ-alkenyl-γ-butyro- or δ-alkenyl-δ-valerolactones are formed by an intramolecular π-allylpalladium displacement process (Scheme 10).

Other reported palladium catalysed couplings that yield functionalised alkenes include: i, the reaction of aryl- or vinylmercurials with vinyl oxetanes, leading to homoallylic alcohols (Scheme 11); ii, the novel allylation of acetals by the action of allyl bromide, aluminium metal, and a catalytic amount of PbBr2 and AlBr3 in tetrahydrofuran; iii, the synthesis of optically active (up to 40% e.e.) dimethyl 2-(4-t-butylcyclohexylidene) methylmalonate through the Pd-catalysed reaction of sodium dimethylmalonate with cis and trans-4-t-butyl-l-vinylcyclohexyl acetate in the presence of chiral phosphines (Scheme 12), and iv, the formation of trans-stilbenes from the palladium catalysed reaction between α-trialkylsilylstyrenes [Ph(R3Si)C=CH2] and arenediazonium tetrafluoroborates [ArN2+BF4-].

Kocienski and his co-workers have employed their previously reported improvement on the Wenkert reaction [i.e. the stereoselective formation of homoallylic alcohols from the coupling of 5- alkyl-2,3-dihydrofurans and Grignard reagents in the presence of Ni(0) catalysts] for the stereoselective preparation of the trisubstituted alkene (4), a key intermediate in a total synthesis of Zoapatanol (5) (Scheme 13). Kocienski et al. have also published the results of a study of the scope and stereochemistry of the Wenkert reaction with 6-alkyl-3,4-dihydro-2H-pyrans. Although the coupling reactions of dihydropyrans are much slower, they are easier to prepare than the corresponding dihydrofurans and are more stable to heat and mild acid. The Wenkert reaction of both dihydropyrans and dihydrofurans was utilised to prepare intermediate (6) in the synthesis of the C(8)-C(20) fragment of premonesin B(7).

Nickel catalysis results in the SN2 allylation of organozinc reagents. On the other hand, high SN2′ selectivity is realised with copper catalysis (Scheme 14).

Stoichiometric use of metals in coupling reactions has been highlighted by Pattenden et al. in their attractive organocobalt chemistry. Thus, cross coupling reactions between two alkenes, leading to a new, functionalised alkene, can be realised by “hydrocobaltation” of one alkene. followed by irradiation of the resulting organocobalt reagent in the presence of the second alkene substrate. Dehydrocobaltation of the coupled species then yields functionalised E-alkenes (Scheme 15). A similar coupling between organocobalt reagents prepared from alkyl halides and styrene has been reported contemporaneously by Branchaud.

Allyltin reagents readily react with pyridines activated by alkyl chloroformates to give α-allylated 1,2-dihydropyridines. Substituted allyltin species (e.g. methallyl, crotyl and prenyl) lead to α- and γ-addition. The use of substituted tin compounds confirms that the reactions occur at the γ-position of the tin reagent, indicating the SN2′ character of the reaction.

1-Bromoalkenylzincates (R1R2C=CBrZnR32Li), generated by the reaction of 1,1-dibromoalkenes with lithium triorganozincate at -85°C, undergo alkylation reactions to produce alkenes (R1R2C=CHR3). The yields are reasonable, but the E/Z-stereoselectivity is low.

Terminal alkenes can be synthesised from 1-alkynes by carbocupration, but the incorporation of branched alkyl groups has been problematic. This can now be achieved by preforming branched alkyl heterocuprates (RCuMgx2) in the presence of excess MgBr2.

Brown and his group have continued to exploit and explore the potential for organoboranes in stereospecific alkene synthesis. One paper revealed the results of a study on the preparation of a variety of vinylic organoboranes and their subsequent stereospecific conversion to E– and Z-alkenes. An improved procedure for both the synthesis of E-dialkylvinylboranes and their conversion to Z-alkenes was disclosed. However, vinylalkylbromoboranes, which can also be converted to Z-alkenes, are found to be better reagents (Scheme 16). Brown’s stereoselective preparation of E– and Z-alkenylboronic esters has been reported previously; this year their transposition to alkenes by reaction with organolithiumGrignard reagents, followed by reaction with iodine, has been investigated (Scheme 17). In a subsequent paper vinylic organoboranes were utilised in pheromone synthesis. Chral dialkylvinylboranes can also be prepared from chiral dialkylboranes and alkynes, and these vinylboranes can be converted into chiral alkenes in good chemical and excellent optical yields.

3 Stereoselective. Simultaneous Formation of sp3 and sp2 centres

Claisen Rearrangement. – The basic Claisen reanangement of vinyl ethers derived from secondary alcohols affords γ,δ-unsaturated aldehydes in which the E-isomer predominates. Yamamoto has now demonstrated that the alkene stereochemistry can be controlled by using organoaluminium reagents (Scheme 18). The Z-selectivity conferred by reagent A is attributed to its steric bulk, which disfavours an equatorial disposition for the R group in the presumed chair-like transition state.

1,4- and 1,5-Stereoselection can be realised by sequential stereocontrolled aldol addition to an α,β-unsaturated aldehyde, followed by Claisen rearrangement. For example, 1,5 diastereoselection is demonstrated when the syn-aldol derivative (8) is converted to its E-enolate, which undergoes a Claisen rearrangement in 80% yield with a stereoselectivity of 95:5; the corresponding Z-enolate is equally selective (Scheme 19).

Other developments with the Claisen rearrangement that have been disclosed include: i, the synthesis of a variety of 3-substituted-2-hydroxy-5-methoxy-p-benzoquinones from 5-methoxy-4-(2-propenyloxy) -O-benzoquinones (Scheme 20); ii, an extension of Kurth’s chiral-auxiliary-mediated aza-Claisen rearrangement of ketene N-allyl-N,0-acetals to the diastereoselective construction of C-α quaternary carbons (Scheme 21); and iii, the thermal rearrangement of N-phenylallylimidates (9) with ortho-ester Claisen-like diastereoselectivity (Scheme 22).

[2.3] Wittig Rearrangements. – The techniques of using sulphones to stabilise the α-carbanion in 2,3 Wittig rearrangements has been shown to lend considerable versatility to the reaction; the rearranged sulphones collapse to aldehydes, which can be functionalised as shown in Scheme 23. Brückner, for example, has employed this clever strategy in the synthesis of a fragment of Amphotericin B.

Several research groups have reported significant levels of asymmetric induction under the influence of chiral substituents external to the rearrangement framework. For example, both Brückner and Nakai have shown that dioxolane-protected chiral diols adjacent to the allylic portion efficiently transfer chirality. Nakai has also observed that TBDMS-protected allylic alcohols display similar stereoselectivity. In a macrocyclic system Marshall et al. have demonstrated the effectiveness of a remote alkoxy substituent for directing stereochemistry (Scheme 24). The selectivity is thought to arise from conformational preferences of the macrocyclic ring engendered by the alkoxy group.

The [2,3] Wittig rearrangement of oxazoline or methyl(tri-n-butylstannyl) ethers of α-alkoxy, tertiary allylic alcohols affords remotely functionalised trisubstituted olefins in a diastereoselective manner (Scheme 25). The stereochemistry of the process is directed by the alkoxy external to the sigmatropic framework. The diastereoselectivity is greatest for ethers derived from anti-diols. Kallmerten has employed this approach in the synthesis of the C13-C25 subunit of zincophorin (8).

(Continues…)Excerpted from General and Synthetic Methods Volume 13 by G. Pattenden. Copyright © 1992 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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