General and Synthetic Methods: Volume 7 (Specialist Periodical Reports - General and Synthetic Methods) - Hardcover

Hardcover

ISBN 10: 0851868843 ISBN 13: 9780851868844

Publisher: Royal Society of Chemistry, 1985

Synopsis

Reflecting the growing volume of published work in this field, researchers will find this book an invaluable source of information on current methods and applications.

About this title

From the Back Cover

A series of reviews by leading specialists in their fields which gives systematic and comprehensive coverage of the progress in major areas of research.

Excerpt. © Reprinted by permission. All rights reserved.

General and Synthetic Methods Volume 7

A Review of the Literature Published During 1982

By G. Pattenden

The Royal Society of Chemistry

Copyright © 1985 The Royal Society of Chemistry
All rights reserved.

ISBN: 978-0-85186-884-4

Contents

Chapter 1 Saturated and Unsaturated Hydrocarbons By K. Cooper, 1, 
Chapter 2 Aldehydes and Ketones By S. C. Eyley, 48, 
Chapter 3 Carboxylic Acids and Derivatives By P. R. Jenkins, 96, 
Chapter 4 Alcohols, Halogeno-compounds, and Ethers By R. C. F. Jones, 161, 
Chapter 5 Amines, Nitriles, and Other Nitrogen-containing Functional Groups By G. Kneen, 198, 
Chapter 6 Organometallics in Synthesis, 233, 
Chapter 7 Saturated Carbocyclic Ring Synthesis By T. V. Lee, 310, 
Chapter 8 Saturated Heterocyclic Ring Synthesis By R. C. Brown, 349, 
Chapter 9 Highlights in Total Synthesis of Natural Products By G. Pattenden, 409, 
Author Index, 449, 

CHAPTER 1

Saturated and Unsaturated Hydrocarbons

BY K. COOPER

1 Saturated Hydrocarbons

Although the reduction of halides with lithium aluminium hydride has been known ever since the discovery of the latter, reductions can be slow and the yields can be poor, especially with aromatic halides. Two improved methods of using the reagent have been reported in 1982. By using a clear solution of lithium aluminium hydride in THF, the yields are greatly improved, and by sonicating the reaction mixture, aromatic bromides or iodides are reduced quickly, in excellent yields (70 — 99%).

The radical chain reduction of thioformates, which are generated from tertiary alcohols, with tri-n-butyltin hydride has been reported by Barton and co-workers, and the mildness of tri-n-butyltin hydride as a reducing agent has been nicely demonstrated by the conversion of the bromo-endoperoxide (1) into the endoperoxide (2). The known reduction of nitro-compounds to alkanes, using tri-n-butyltin hydride, has been utilized in the synthesis of the phenylalkyl sulphoxide (6). Thus, Michael addition of the nitroalkane (3) to the αβ-unsaturated sulphoxide (4) furnishes the intermediate nitro-sulphoxide (5), which cleanly gives the sulphoxide (6) in high overall yield ( > 60%).

The combination of tetrakis(triphenylphosphine)palladium and lithium triethylborohydride is an effective reagent for the removal of allylic ethers, sulphides, sulphoxides, sulphones, and silyl ethers, and the stereochemical integrity of the double-bond is maintained. A preliminary report has appeared on the use of tetra-alkylammonium graphite lamellar compounds as electron reservoirs, and thus as reagents for reductive dehalogenation. The graphite compound is built up by electrochemical means, and on completion of the reduction it may be filtered off and re-used. Enol triflates, which are readily prepared from ketones, undergo rapid hydrogenolysis to give the corresponding alkanes in high yield (65 — 90%), and the transfer hydrogenation of aromatic nitriles (using ammonium formate as the hydrogen source, with palladium on charcoal as the catalyst) gives the corresponding methyl compounds (Scheme 1). A range of additional functionality is tolerated in the aromatic ring, but the reaction fails for aliphatic nitrites.

The generation of uranium trichloride in situ, by the reaction of uranium tetrachloride with lithium hydride or lithium aluminium hydride, catalyses the reduction of alkenes by lithium hydride or lithium aluminium hydride, but the reaction is at present limited to simple olefins. Nakao has reported that the supported catalyst that is made by immobilizing colloidal nickel boride on magnesium hydroxide exhibits much higher activity for hydrogenation of olefins than the previously reported sol-type catalyst. The isoprenoid alkane (8) appears in a variety of marine surface sediments, and its structure has been confirmed by total synthesis, employing the straightforward hydrogenation of the olefin (7) (Scheme 2). Hydrogenation of allylic and homoallylic alcohols with asymmetric induction can be achieved when chelate bis-phosphine rhodium complexes are used (Scheme 3). The asymmetry can be rationalized by using a model where the non-bonded interactions that are experienced by the methyl group in the transition-state are minimized. The combination of hydroxylamine and ethyl acetate generates di-imide in a straightforward fashion, and affords a new method of performing reductions with di-imide.

Alkyl methyl ketones are alkylated reductively with optically active isobutyl-aluminium dichloride in benzene to give optically active phenylalkanes, although the enantiomeric excesses are low (Scheme 4); the reductive vinylation of carbonyl compounds has been accomplished by addition of β-trimethylsilyl-ethyl-lithium to the carbonyl compound (9) followed by protodesilylation of the intermediate (10). The palladium-promoted alkylation of some alkenes, using a chiral ligand and a racemic nucleophile or a chiral sulphoxide, leads to alkanes after reductive cleavage of the intermediate σ-complexes, as outlined in Scheme 5. The chemical yields of products were poor (20 — 30%) and the optical purities were only moderate (up to 40%).

Diferrocenyl- and diaryl-carbinols (11) are reductively coupled when their corresponding lithio-derivatives are treated with titanium trichloride, giving high yields (70 — 80%) of the ethanes (12), whereas electroreductive dimerization of phenyl bromoacetic esters gives mixtures of meso- and (R,S)-succinates in moderate yield (50%) (Scheme 6). α, ω-Di-iodides (13) react with t-butyl-lithium at low temperature to give the cycloalkanes (14) in excellent yields (85 — 98%), and the reaction can be viewed as an initial metal–halogen exchange followed by a Wurtz coupling. Although the corresponding dibromides do not react cleanly, the first synthesis of [1,1,1]propellane (16) has been accomplished, by treatment of the dibromide (15) with t-butyl-lithium; the propellane is a fairly stable compound, with a t1/2 of 5 minutes at 114 °C.

2 Olefinic Hydrocarbons

Methylenetriphenylphosphorane has found wide use in the synthesis of terminal olefins but gives low yields when applied to hindered ketones. Corey and Kang have now shown that the phosphorane is deprotonated to give the lithio-derivative (17), which is a highly reactive ylide reagent, reacting with hindered ketones, epoxides, and aldehydes as outlined in Scheme 7. The Wittig reaction can be carried out by a solid-liquid transfer process, giving high yields of alkenes (70 — 95 %) (Scheme 8), and the anions of Wittig reagents (18) are trapped with methyl chloroformate to give the stable Wittig equivalents (19). By heating (19) in the presence of aldehydes, the corresponding olefins (20) are formed in high yield (70 — 80%); ylides or carbonyl compounds with α-hydrogen atoms, however, cannot be used in this method.

Phosphinothioic amides are highly effective reagents for the alkylidenation of ketones, and the method has been developed as a means of methylenation coupled with optical resolution. The reaction of the anion of the phosphinothioic amide (21) gives the diastereoisomeric mixture (22), which, after separation, can be converted into the optically active olefins (23). The method has been applied to the synthesis of the (+)- and (-)-iridoid monoterpene hop ether (24), and can be extended to alkylidenation with resolution.

The reaction of alkenyldi-isobutylalane with titanocene dichloride gives dimetalloalkanes (25), which convert ketones into olefins (26) in good yield (around 65 %) but with only poor stereoselectivity; the general use of heavy main-group elements in the synthesis of terminal olefins and of (Z)- and (E)-olefins stereospecifically has been reviewed by Kauffmann.

An interesting method for the introduction of the isopropylidene moiety has been described, using keten thioacetal chemistry. Thus, the reaction of the enolate of ketone (27) with carbon disulphide followed by methylation gives the keten thioacetal (28). Double conjugative addition and elimination, using lithiodimethyl cuprate, then affords the isopropylidene ketone (29). Similar methodology has been used to convert thioketen acetals into mono-, di-, or tri-substituted olefins with high stereospecificity by addition of Grignard reagents, under nickel catalysis. 1,3-Bis(diphenylphosphino)propanenickel dichloride is the catalyst of choice for introduction of an alkyl group with E stereospecificity (where possible), and the combination of triphenylphosphinenickel dichloride and isopropylmagnesium bromide allows the introduction of a hydrogen atom, again with E stereospecificity (Scheme 9).

Further studies on the cationic prenylation of olefins have been published; these studies also demonstrate the range of nucleophilicity that is required in the reaction. Nitroalkanes (30) can be C-allylated under Pd0 catalysis, where the reactivity of the allylic component (31) is in the order X = OPh > OAc > OH.

The Lewis-acid-catalysed reaction of allyltrimethylsilane with the carbinols (32) gives the corresponding allyl compounds (34) in good yield ( > 60 %). A similar result can be achieved by the Lewis-acid-catalysed rearrangement of the allyldimethylsilyl ethers (33), presumably via the intermediate (35).

Since an early report that primary halides do not undergo elimination to give terminal olefins, no further reports of such attempts have appeared. Wolff and Agosta have now reported that the treatment of β-disubstituted primary iodides with DBU or DBN efficiently produces 1,1-disubstituted olefins (Scheme 10). The elimination of secondary and tertiary bromides using DBU, which gives predominantly the Saytzeff product, has also been studied, and secondary alkyl primary amines (36) react with the pentacyclic pyrylium salt (37) to give mixtures of olefins (38) directly at 20 °C. The mixtures are thought to arise from carbonium-ion rearrangements.

Two new modifications of the synthesis of olefins from vicinal diols have appeared in the literature. Barua and Sharma have demonstrated that both cis- and trans-secondary-tertiary 1,2-diols are readily converted (in a mild manner, and in excellent yields) into olefins by using chlorotrimethylsilane and sodium iodide in acetonitrile at room temperature. Corey and Hopkins have improved the thionocarbonate olefin synthesis by modification of the reaction conditions to allow sensitive and complex diols to be converted into olefins. Thus, the reaction of 1,2-diols with thiophosgene affords the thionocarbonates (39) in excellent yields ( > 86 %), and subsequent syn-elimination is achieved by warming with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine (40), giving the olefins (41) in high yield ( > 70 %).

Vicinal dibromides are readily converted into olefins under very mild conditions, using zinc and a catalytic amount of titanium tetrachloride in THF. The reaction exhibits anti stereoselectivity, and is high-yielding, ( > 80%). Thiophen-2-tellurolate ion, generated in situ by the reaction of sodium boro- hydride with a catalytic amount of the ditelluride (42), also debrominates vicinal dibromides with anti stereospecificity, in excellent yields ( > 90%) (Scheme 11).

Ethyl trimethysilylacetate is converted into 1,1-disubstituted olefins in high yield (~80%) by the addition of two equivalents of Grignard reagent, followed by treatment of the resulting β-hydroxysilanes with acid; thus (43) can be considered as a vinyl dication synthon (Scheme 12).

Full details of the cycloelimination of β-silylethyl sulphoxides to give olefins have appeared, and β-trimethylsilyl sulphoxides can also be used in an alternative synthesis of olefins. Thus, elimination of sulphenic acid from (44) followed by protodesilylation of the mixture of olefins (45) and (46) affords the (Z)-/(E)-olefins (47) regiospecifically, in excellent yield (80 %). The trimethysilyl ethynynl sulphone (49) has been developed as a vinyl cation synthon by Barr and co-workers. The addition of carbanions (48) to the synthon (49) furnishes the vinyl sulphones (50), which can be converted into the adducts (51) either by reduction, or, where sensitive functionality is present, by formation of a cyanhydrin before reduction. In Kocienski's synthesis of diumycinol (52) the 6,7 and 11,11' double-bonds were formed by the previously reported reductive elimination of β-substituted sulphones. Vinyl sulphones can be prepared stereospecifically, and Julia and his group have reported an alternative to the reductive removal of the sulphonyl group from vinyl sulphones which is completely regiospecific. It comprises the treatment of vinyl sulphones with sodium dithionite in the presence of sodium bicarbonate. The coupling of Grignard reagents with vinyl sulphones under nickel or iron catalysis also allows the synthesis of trisubstituted olefins with defined stereochemistry, in good yield (60 — 70%) (Scheme 13).

The Ramberg–Bäcklund reaction of α-halo-sulphones to give olefins is a versatile reaction, and the use of phase-transfer -catalysis permits far more diverse functionality to be incorporated in the starting materials (Scheme 14). The related extrusion of selenium from selenides and diselenides by pyrolysis to give dibenzyl olefins and related compounds has been studied by Misumi's group.

The field of borane chemistry has seen some significant advances during 1982, and several syntheses of natural products have appeared, utilizing the new applications, mostly due to the work of Brown and co-workers. By its reaction with alkenes and subsequent reduction, t-hexylchloroborane is converted into the unstable t-hexyl(alkyl)boranes (53), which then add to 1-halogeno-1-alkynes to give t-hexyl(α-halovinyl)boranes (54). Rearrangement of (54) with sodium methoxide allows the transfer of the alkyl group from borane to carbon with complete stereospecificity, affording (after acid hydrolysis) the (E)-alkenes (55) in excellent overall yield (70 — 80%). (E)-Alkenes are also produced stereospecific ally by the reaction of the alkylbromoboranes (56) with bromo-alkynes and subsequent transfer of the alkyl group and hydrolysis. 50 The alkylbromoboranes (56) also react with terminal alkynes to give alkyl(bromo)vinylboranes (57), which rearrange to (Z)-olefins (58) in good yields; the method has been applied to a synthesis of muscalure (59). An interesting modification of this method, using borepan (60), allows the synthesis of (Z)-alk-7-en-1-ols. One end of the cycloalkane chain in the (E)-alkenylborepan (61) migrates to the adjacent carbon, giving the intermediate (62), which on oxidation furnishes the alkenols (63) in excellent yields ( > 80%). Internal acetylenes (65) are converted into trisubstituted olefins (67) by their reaction with dialkylboranes (64) and the rearrangement, mediated by sodium methoxide and iodine, of the intermediates (66). The method allows the synthesis of alkenes of defined stereochemistry, but at present has only been applied to symmetrical alkynes. However, the addition of (68) to bromoalkynes forms the basis of a synthesis of trisubstituted alkenes in which both alkyl groups on boron are transferred to the alkyne, using the methodology outlined in Scheme 15. The method is restricted by the availability of the dialkylboranes. Midland and Preston have reported the synthesis of homoallylic alcohols (71) with a high degree of enantio- and diastereo-selectivity. The condensation of aldehydes with enantiomerically enriched allylboranes (70), which are formed by hydroboration of optically active propargyl acetates (69) with dialkylborane followed by base-induced rearrangement, gives predominantly the threo-homoallylic alcohols (71).

The research groups of Fujisawa and Mori have both published independent stereospecific syntheses of (Z)- and (E)-trogodermal. The copper-catalysed cis-addition of [he Grignard reagent (72) to acetylene, followed by coupling with the iodide (73) and SN2'-type ring-opening of δ-vinyl-δ-valerolactone (74), were used by Fujisawa et al. to introduce the (Z)- and (E)-double-bonds, respectively. Mori and co-workers, however, used the common intermediate (75), prepared in several steps from β-citronellic acid, to gain access to both double-bonds, and the synthesis is an improvement on a previously published report (Scheme 16).

(Continues...)

Excerpted from General and Synthetic Methods Volume 7 by G. Pattenden. Copyright © 1985 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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Edition details

• Publisher: Royal Society of Chemistry
• Publication date: 1985
• Language: English
• ISBN 10: 0851868843
• ISBN 13: 9780851868844
• Binding: Hardcover
• Number of pages: 482
• Editor: G Pattenden