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 6

A Review of the Literature Published During 1981

By G. Pattenden

The Royal Society of Chemistry

Copyright © 1983 The Royal Society of Chemistry
All rights reserved.
ISBN: 978-0-85186-874-5

Contents

Chapter 1 Saturated and Unsaturated Hydrocarbons By J. M. Clough, 1,
Chapter 2 Aldehydes and Ketones By S. C. Eyley, 56,
Chapter 3 Carboxylic Acids and Derivatives By P. R. Jenkins, 98,
Chapter 4 Alcohols, Halogeno-compounds, and Ethers By R. C. F. Jones, 154,
Chapter 5 Amines, Nitriles, and Other Nitrogen-containing Functional Groups By G. Kneen, 193,
Chapter 6 Organometallics in Synthesis, 218,
Chapter 7 Saturated Carbocyclic Ring Synthesis By D. W. Knight, 277,
Chapter 8 Saturated Heterocyclic Ring Synthesis By R. C. Brown, 312,
Chapter 9 Highlights in Total Synthesis of Natural Products By A. P. Johnson, 371,
Author Index, 395,

CHAPTER 1

Saturated and Unsaturated Hydrocarbons

BY J. M. CLOUGH

1 Saturated Hydrocarbons

Several new and improved methods for the reductive removal of functional groups have been presented during the year. Extending a process developed for the reduction of secondary alcohols, Barton and his co-workers have shown that primary akohols, derivatized as xanthate or thiobenzoate esters, or as thiocarbonyl imidazolides, are deoxygenated without competing Chugaev elimination on treatment with tri-n-butyltin hydride at 130–150 °C. Selective derivatization of primary hydroxyl groups is straightforward, enabling them to be removed without affecting secondary hydroxyl or other functional groups. Primary and secondary alcohols, or their methyl or trimethylsilyl ethers, are conveniently deoxygenated via the corresponding iodides generated in situ by successive treatment with sodium iodide, chlorotrimethylsilane, and zinc. Diaryl- or triarylmethanols are reduced to the corresponding arylmethanes on refluxing with iron pentacarbonyl and benzoyl chloride in mesitylene.

A mixture of sodium borohydride and palladium chloride reduces aryl ketones and benzyl alcohols to the corresponding hydrocarbons. Carboxylic acid esters and non-activated hydroxyl groups are not affected by this new reducing system, but ketones are reduced to alcohols, and aromatic chlorine atoms are removed. Bis(benzoyloxy)borane, prepared in situ from BH3·THF and benzoic acid, is a convenient alternative to catecholborane for the reduction of the tosylhydrazone derivatives of aldehydes and ketones to hydrocarbons under mild conditions. Ketones that are relatively unhindered can be deoxygenated in the gas phase at 190 °C in the presence of hydrogen over a nickel–alumina catalyst. The main drawback of the method is the lack of selectivity: other functional groups are also lost under the reaction conditions. A mixture of sodium borohydride and cerium trichloride in methanol at room temperature fully reduces the carbonyl group of thiochromones to give the corresponding thiochromenes (Scheme 1). Chromones or their thiones remain unchanged under these reaction conditions.

Non-activated primary, secondary, or tertiary alkyl fluorides (as well as chlorides) are reduced in high yield to hydrocarbons by a solution of potassium and dicyclohexyl-18-crown-6 in diglyme or toluene at ambient temperature. Organotin hydrides can be supported on inorganic carriers like alumina or silica, enabling alkyl halides to be reduced under heterogeneous conditions. As an alternative to its use in dipolar aprotic solvents, sodium borohydride can be used to reduce alkyl chlorides, bromides, and iodides as well as sulphonate esters to alkanes under phase-transfer conditions. Dichloromethane solutions of the readily-available reagents P2I4 and PI3 reductively remove the halogen from α- iodo- and α-bromo-ketones, usually at room temperature and in high yield.

The research groups of Tanner and Ono have independently reported that tertiary and some secondary nitro groups are removed by reduction with tri-n-butyltin hydride in the presence of a radical initiator. Keto, ester, cyano, phenylthio, and primary nitro groups remain unchanged under the reaction conditions.

The sulphonyl group of α nitrosulphones is replaced by hydrogen on treatment with N-benzyl-1,4-dihydronicotinamide (BNAH) in deoxygenated DMF (Scheme 2). Keto and cyano groups are not affected. In the presence of a catalytic amount of azobis(isobutyronitrile), or under irradiation, BNAH also reduces alkylmercury(II) acetates to alkanes.

Olah and his co-workers have discovered that the reducing ability of magnesium in methanol is dramatically enhanced by the addition of a catalytic amount of palladium metal on carbon; even non-activated multiple carbon–carbon bonds are rapidly and completely reduced under these reaction conditions.

Following their recent disclosure of a three-step process for the replacement of oxygen in ketones by two methyl groups, Reetz and his co-workers have now shown that the transformation can be accomplished directly by treatment of the ketone with dimethyltitanium dichloride. Smooth geminal methylation occurs even when the product has two neighbouring quaternary carbon atoms, e.g. the terpene ‘cuparene’ (1). Methyltitanium chlorides (prepared from dimethylzinc and titanium tetrachloride in suitable proportions), or dimethylzinc and catalytic quantities of titanium tetrachloride, also methylate t-alcohols, t-ethers, t(reported in 1980) and s- (but not primary-) alkyl chlorides, and gem-dihalides (e.g. Scheme 3).

Metzger et al. have examined the addition of alkanes to a representative selection of activated, non-activated, and de-activated olefins at high temperature (650 — 723 K) and under high pressure (ca. 200 bar). Yields are strongly dependent on the reaction conditions and the olefin: alkane ratio, but regioselectivity, which seems to be controlled mainly by steric rather than electronic factors, is remarkably high in some cases, e.g. Scheme 4.

The free radicals generated by treating t-butyl, allyl, or benzyl halides with three equivalents of chromous chloride couple to form symmetrical dimers. Alternatively, a careful choice of reaction conditions enables good yields of cross-coupled products to be prepared, e.g. (2)->(3).

Benzyl chlorides and bromides undergo reductive coupling at room temperature and under neutral conditions on treatment with a small excess of chlorotris(triphenylphosphine)cobalt(I), e.g. (4) -> (5). Benzal bromide gives E-stilbene under the same conditions. Alternatively, benzyl, alkyl, and aryl chlorides, bromides, and iodides can be reductively coupled by using lithium in tetrahydrofuran under the influence of ultrasound. Little or no reaction occurs in the absence of sonic waves. Long straight-chain iodoalkanes (e.g. 1-iodotetradecane) undergo reductive coupling to give n-alkanes on treatment with hydrazine and a catalytic amount of palladium, but yields fall dramatically with shorter substrates.

Larock and Leach have described the first general method for the alkylation of a wide variety of organomercurials. For example, primary alkylmercurials cross-couple with alkylcuprates to give moderate yields of alkanes, e.g. (6)->(7); reactions involving secondary alkylmercurials are less efficient. [1,3-Bis(diphenylphosphino) propane] nickel(II) chloride catalyses the cross-coupling of alkylmagnesium halides or alkylalanes with arylphosphates to furnish aryl-alkanes in high yields (e.g. Scheme 5). Lipschutz and his co-workers have reported that the mixed cuprates prepared from cuprous cyanide and two equivalents of an alkyl- (or vinyl-) lithium are highly reactive species; they smoothly couple at low temperatures even with unactivated secondary alkyl bromides and iodides to give hydrocarbons (Scheme 6). Though less reactive, secondary alkyl tosylates are also suitable substrates, but secondary alkyl chlorides and mesylates are almost inert.

2 Olefinic Hydrocarbons

Several research groups are exploring synthetic routes to tetra-t-butylethylene, regarded as the ultimate sterically-hindered olefin, and a number of new ‘tied back’ relatives have been described. Warner and Jacobson and their co-workers have shown that the gem-dibromocyclopropane (8) undergoes carbene dimerization on treatment with methyl-lithium to give, albeit in low yield, the olefin (9). Spectroscopic data indicate that there are no severe non-bonded repulsions in (9), and that the double bond is planar. The groups of Guziec and Krebs have described syntheses of the hindered olefins (10), (11), and (12). Conversion of (10) into tetra-t-butylethylene itself failed when functionalization of the aromatic rings could not be achieved without cleavage of the double bond.

Convincing evidence for the existence of methylenecyclopropene has been provided by trapping it in the form of a [4 + 2] cycloadduct for the first time; treatment of the sulphonium salt (13) with sodium cyclopentadienide furnished the hydrocarbon (14) in 13% yield.

Adam and his co-workers have shown that sterically congested E-olefins are conveniently prepared by the β-lactone route shown in Scheme 7. Stereocontrol is achieved because α-lithiocarboxylates condense with aldehydes and ketones to give β-hydroxy acids of predominantly threo-configuration; once formed, dehydrative cyclization is straightforward because the bulky substituents force the carboxy and hydroxy groups into juxtaposition.

Bicyclic bridgehead olefins with a carbonyl group in the largest bridge can be constructed by oxy-Cope rearrangement of 3-hydroxy-1,5-dienes of types (15) and (16). Considerable interest has been shown in the strained bicyclic enone (17) and several independent syntheses have been reported.

Umani-Ronchi and his co-workers have prepared various new active metals that consist of highly dispersed palladium or nickel on graphite and which selectively catalyse the semi-hydrogenation of acetylenes to Z-olefins. A different catalyst for the same process can be prepared by successive treatment of chloromethylated polystyrene beads with anthranilic acid and palladium chloride. Alternatively, acetylenes can be reduced to Z-olefins by a catalytic transfer process using sodium phosphinate as the hydrogen donor and an easily prepared lead- or mercury-modified palladium catalyst.

Demerseman and Dixneuf have reported that acetylenes react with Cp2Ti(CO)2 in wet hexane to give vinyltitanium complexes (18), the vinylic hydrogen atoms originating from water (Scheme 8). Cleavage of the carbon-titanium bonds by aqueous acid is stereospecific, releasing Z-olefins (19).

Vinyl sulphides are cleanly reduced to the corresponding olefins without stereomutation or over-reduction by 2-propylmagnesium bromide and a catalytic amount of bis(triphenylphosphino)nickel(II) chloride. Acetals, ethers, aromatic systems, and isolated olefins are compatible with these reaction conditions.

In a mild alternative to the Hofmann elimination, acrydinium salts (20), prepared from the corresponding pentacyclic pyrilium salt and primary amines, are converted into terminal olefins (21) on heating with the non-nucleo-philic base triphenylpyridine. Small quantities of 2-alkenes are formed as by-products.

Acid-sensitive t-alcohols can be dehydrated by a process that is related to the Chugaev reaction but which takes place at much lower temperatures (refluxing THF) (Scheme 9). vic-Diols react with iodoform, triphenylphosphine, and imidazole to give the corresponding olefin, probably via reductive elimination from a di-iodo intermediate; this method is particularly useful for preparing unsaturated sugars.

vic-Dibromides and dichlorides are dehalogenated to give olefins in almost quantitative yields on treatment with sodium sulphide in DMF at room temperature.

Clive and Kalè have shown that β-oxygenated selenides, sulphides, and iodides are smoothly and stereospecifically converted into olefins on treatment with chlorotrimethylsilane and sodium iodide in acetonitrile, e.g. (22)->(23). A specific use for this transformation is the reversal of various cyclofunctionalization processes, allowing them to be used to protect at the same time a double bond and an attached nucleophile, e.g. (24)->(25). A related use for chlorotrimethylsilane and sodium iodide in acetonitrile is the stereospecific deoxygenation of oxirans to give olefins, e.g. Scheme 10.

Primary alkyl phenyl tellurides undergo elimination to form terminal olefins in high yields on treatment with an excess of N-chloro-N-sodio-4-methylbenzenesulphonamide (chloramine-T) in refluxing THF.

vic-Dinitro compounds and β-nitrosulphones are converted into olefins via free-radical elimination processes on treatment with tributyltin hydride in the presence of catalytic quantities of azobis(isobutyronitrile) (AIBN). Elimination from the dinitro compounds shows no stereocontrol; by contrast, elimination from β-nitrosulphones is highly stereoselective, e.g. (26)->(27), presumably because elimination from the intermediate radical is faster than rotation about the central carbon–carbon bond.

γ-Trimethylsilyl t-alcohols (28) undergo a carbonium ion rearrangement under acidic conditions with a phenyl or hydride shift and loss of the silyl group. Competing hydride and alkyl shifts are observed with alcohols (28) in which R1 is an alkyl group.

The Horner modification of the Wittig reaction, in which a diphenylphosphinoyl group is the anion-stabilizing f unction, can be used to prepare olefins of either E– or Z-geometry. Reaction of a lithiated alkyldiphenylphosphine oxide with an aldehyde gives predominantly the erythro-alcohol (29) (precursor of the Z-olefin), whereas successive acylation and reduction gives predominantly the threo-alcohol (30) (Scheme 11).

Baker and Sims have shown that addition of a catalytic quantity of 15-crown-5 to a Wadsworth–Emmons reaction greatly facilitates olefin formation. For example, reaction between the aldehyde (31), phosphonate (32), and sodium hydride in the presence of 15-crown-5 gave the heterocyclic stilbene analogue (33) (45% : the key step in a synthesis of the furanosesquiterpene pallescensin-E).

[(Phenylthio)methyl]carbinyl benzoate esters, e.g. (34), easily prepared from ketones, undergo reductive elimination to give high yields of olefins, e.g. (35) on treatment with titanium metal in refluxing THF (Scheme 12).

Kauffmann and his co-workers have developed a series of titanium or chromium reagents (Me3SiCH2TiCl3, Me3SiCH2CrCl2, Me3GeCH2TiCl3) which selectively methylenate aldehydes in moderate to high yields e.g. Scheme 13; ketones react to only a very small extent or not at all. The reagents are easily generated in situ by treatment of the corresponding magnesium compounds with TiCl4 or CrCl3.

The first method for preparing alkylidene-bridged bimetallic complexes with bridging groups other than methylene e.g. (36) has been discovered, and pre-liminary experiments have shown that these too are capable of converting ketones into olefins, e.g. cyclohexanone -> (37), and esters into vinyl ethers.

Aromatic aldehydes or ketones can be coupled to give stilbenes by the low-valent titanium method without affecting carboxylate, tosylate, or halo-aromatic substituents in the substrates.

A synthetic sequence has been discovered in which aldehydes which are not branched at the α-position undergo formal reductive dimerization to give symmetrical olefins (e.g. Scheme 14). At the key step, α-stannylalkyl halides, which are stable and easily handled, smoothly couple on treatment with n-butyl-lithium under very mild conditions (–78 to 0 °C). Furthermore, the difference in reactivity between α-stannylalkyl iodides and chloride& enabled a moderate yield of a cross-coupled olefin from two different aldehydes to be obtained. α-Branched aldehydes exhibit a different pattern of reactivity, furnishing terminal olefins instead of coupled products (Scheme 15), probably for steric reasons.

Mol and his co-workers have reported that self -metathesis of ω-olefinic nitrites (to give unsaturated dinitriles) and co-metathesis between ω-unsaturated nitrites and olefins (to give new unsaturated nitriles) can be achieved with the catalytic system WCl6–Me4Sn.

(Continues…)Excerpted from General and Synthetic Methods Volume 6 by G. Pattenden. Copyright © 1983 The Royal Society of Chemistry. Excerpted by permission of The Royal Society of Chemistry.
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