Aliphatic Chemistry Volume 5

A Review of the Literature Published During 1975

By A. McKillop

The Royal Society of Chemistry

Copyright © 1977 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-602-4

Contents

Chapter 1 Alkanes, Acetylenes, Allenes, and Olefins By J. C. Saunders and B. P. Swann, 1,
Chapter 2 Functional Groups other than Alkanes, Acetylenes, Allenes, and Olefins By E. F. V. Scriven, 80,
Chapter 3 Naturally Occurring Polyolefinic and Polyacetylenic Compounds By G. Pattenden, 201,
Chapter 4 Chemistry of the Prostaglandins By K. B. Mallion, 240,
Chapter 5 Fatty Acids and Related Compounds By F. D. Gunstone, 290,
Author Index, 319,

CHAPTER 1

Alkanes, Acetylenes, Alienes, and Olefins

BY J. C. SAUNDERS AND B. P. SWANN

1 Alkanes

Synthesis of Alkanes. — Several new methods for the reductive removal of halogens from aralkyl halides have been discovered. A titanocene dichloride-magnesium system reduces straight-chain alkyl halides in good yield. The ‘ate’ complex prepared from 9-borabicyclo[3,3,1]nonane (9-BBN) and n-butyl-lithium selectively reduces tertiary alkyl, benzyl, and allyl halides. The hydridotetracarbonylferrate anion is a convenient reagent for halogen replacement in polyfunctional molecules such as (1) where normal reducing agents would attack the anhydride group. A similar transformation can be achieved electrochemically in the presence of certain aromatic hydrocarbons such as naphthalene, which function as catalytic electron-transfer reagents. A full paper on the reductive coupling of allylic and benzylic alcohols to hydrocarbons using titanium trichloride-lithium aluminium hydride has appeared. In reactions of alkyl halides in 1,2-dimethoxyethane with sodium (Wurtz coupling) conventional SN2 processes are excluded by the observation of no discrimination against the formation of bineopentyl from neopentyl iodide.

Alkanes are formed in good yield when dilute solutions of non-activated carboxylic esters are irradiated at 254 nm in hexamethylphosphorictriamide (HMPA)–H2O (95:5). Conversion of ketones into the corresponding toluene-p-sulphonylhydrazone followed by reduction with the commercially available catecholborane gives the corresponding alkane and provides a convenient mild alternative to the vigorous basic conditions of the Wolff–Kishner reaction (Scheme 1).

Reactions of Alkanes. — Homogeneous catalytic activation of C—H bonds has been reviewed and further work has been done on the rhodium trichloride-catalysed isotopic exchange of hydrogen in alkanes. Results suggest the reaction proceeds via a terminal abstraction π-complex as do similar platinum and iridium systems.

Benzene has been alkylated with C1-5 alkanes in anhydrous fluoroantimonic acid, showing the ability of this system to ionize alkanes to alkylcarbenium ions even in the presence of benzene. Small quantities of alkenes catalyse the reaction. Selectivity in the chlorination of alkanes with N-chloroamides has been examined and several abstracting species are involved depending on the reaction conditions.

The use of ozone absorbed onto silica gel at low temperatures (up to 4.5% by weight at -78 °C) avoids the normal solubility problems associated with ozone in organic solvents. This reagent has been conveniently used to convert in high yield alkanes with tertiary carbons [e.g. (2)] into the corresponding tertiary alcohols. Irradiation of solutions of ozone in alkanes with visible light results in the formation of products derived from the rearrangement of ozone-hydrocarbon complexes, whereas irradiation with u.v. light leads to products derived both from rearrangement of the complexes and attack of singlet oxygen on the hydrocarbon. A similar study has been made on the photolysis of nitrous oxide in hydrocarbons, and again both singlet and triplet oxygen states were found to be involved. New oxygen-activating systems for the direct hydroxylation of hydrocarbons at ambient temperatures include those containing iron(II) chloride–hydrazobenzene–carboxylic acid–oxygen mixtures which are supposed to generate a strongly polarized peroxidic form which is active in this type of transformation.

α- and β-Cyclodextrins allow shifts in the n.m.r. spectra of hydrocarbon substrates to be seen where lanthanide-shift reagents or aromatic solvent shifts are of no value. Examples reported include the spectra of p-cymene and adamantane, both of which were run in D2O.

2 Acetylenes

Amongst books and reviews covering aspects of acetylene chemistry are articles on the chemistry of diacetylenes and several extensive mentions of acetylenes in cycloaddition reactions, as well as electrophilic and nucleophilic reactions. The interest in acetylene–metal complexes continues unabated and reviews include diyne reactions via transition metal complexes to give new compounds, homogeneous activation of alkynes and alkenes by metal complexes, the role of π-complexes in the carbometallation of alkynes by boron and aluminium alkyls, and the oligomerization of alkynes and olefins and their use in synthesis using nickel complexes.

Synthesis of Acetylenes. — Potassium 3-aminopropylamide, a readily prepared stable ‘superbase,’ induces the migration of internal triple bonds to the terminus of the carbon chain within seconds at 0°C. Evidence based on exchange studies shows it to be as reactive as caesium cyclohexylamide in cyclohexylamine. A procedure has been described for the alkylation of monolithium acetylide to give terminal acetylenes in good yield. The dilithium salt (3) will add electrophiles regiospecifically, initially at the propargylic carbon centre. (Scheme 2). In the synthesis of 1-alkynes from bromoalkanes using monolithium acetylide isomerization to the 2-alkyne was found to occur under milder conditions than had been reported previously; excess acetylide and long reaction times favour this process. Sodio-1-alkynes react with allyl chlorides in liquid ammonia to give mixtures of allylated products. A convenient preparation of amine-free monolithium acetylide has been reported, as has its subsequent transformation to ethynyl carbinols by reaction with aldehydes and ketones.

Various palladium catalysts for performing Castro–Stephens coupling reactions at room temperature have been described. 4-Substituted 2,6-di-iodophenols and copper(i) phenylacetylide have been used to prepare iodinated 2-arylbenzofurans as potential thyroxine analogues following Castro’s procedure. Highly fluorinated acetylenes have been prepared by a copper powder-DMF coupling procedure from vinyl halides and polyfluoro-iodides, followed by a bromination–dehydrobromination sequence. Vinylcopper compounds react smoothly with a variety of 1-halogeno-alkynes under mild conditions to give conjugated enynes in high yields.

A combination of trimethylsilyl chloride and magnesium in HMPA converts phenylacetylene into trimethylsilylphenylacetylene. A new route to the insect attractant propylure utilizes lithium tripropyl(trimethylsilylethynyl)borate as a key reagent in this synthesis (Scheme 3). Silyl-protected functionalized penta-1,3-diynes can be prepared by the route shown in Scheme 4.

The preparation of 5,8,11-dodecatriynoic acid via a Grignard coupling of 1-bromo-2,5-hexadiyne and 5-hexynoic acid, and its further conversion into 5,8,11,14-eicosate-traynoic acid (TYA) and thence to arachidonic acid has been described. The route can also be adapted to the synthesis of novel methylated arachidonic acids. The unstable copper(I) trimethylsilylacetylide (4) has been synthesized from copper(I) t-butoxide and trimethylsilylacetylene; (4) reacts with acid chlorides to give trimethylsilylethynyl ketones. Dilithium trialkynylcuprates in the presence of HMPA add to cyclic α,β-unsaturated ketones by a regiospecific 1,2-addition. A method was reported last year for effecting the corresponding 1,4-addition.

n-Butyl-lithium converts 1-chloro-2-ethoxytetradecane to the acetylene by a dual elimination. Treatment of 2-chloronorbornene with butyl-lithium followed by quenching of the reaction mixture with D2 gives some evidence for norbornyne as a highly strained intermediate. Lithium diphenylphosphide dehydrobrominates 1,2-dibromoalkenes to acetylenes in moderate yield; in contrast, the 1,2-dichloroalkenes give mainly substitution products. A new synthesis of diphenylacetylenes involves the reaction of benzyl-NNN’N’-tetramethyl phosphorodiamidite with benzotrichloride followed by base treatment and elimination. The synthesis of 1,5-cyclo-octadiyne in 2% overall yield from butatriene is reported in full.

Pyrolysis of 5-arylidene-2,2-dimethyl-1,3-dioxan-4,6-diones (5) through a silica tube gives arylacetylenes in good yield. 2,4-Dinitrobenzenesulphonyl hydrazine is superior to toluene-p-sulphonylhydrazine, and gave a cleaner reaction, in the Eschenmoser cleavage of (6). Further attempts to prepare dimethoxyacetylene by the pyrolysis of adducts such as (7) have been unsuccessful. Mass spectrometric studies indicate that for X=C1, elimination occurs to give tetrachloroanthracene, but the fate of the bridgehead was extrusion as methoxycarbyne. Full details on the preparation of acetylene dicarbonyl fluoride have been published and its reactions with alcohols, thiols, and amines studied. Alcohols and thiols give the expected products; under neutral conditions aniline gives the isomaleimide (8a) whereas the normal maleimide (8b) is produced under acidic conditions. Secondary and primary aliphatic amines give the straight-forward bisacetylenic amides. Silver phenylacetylide and aryldiazonium salts give arylazoethynylbenzenes in improved yield over previous procedures.

Ketones react with organozinc derivatives of propargylic bromides to give mixtures of β-acetylenic and α-allenic alcohols; with the corresponding magnesium derivatives the major product is the β-acetylenic alcohol. The addition of these organometallic reagents to benzaldehyde imines is quite stereoselective with the threo-isomer predominating (Scheme 5). Despite previous reports to the contrary, 1-bromoallenes can be readily converted into Grignard reagents by reaction with magnesium: reaction of the Grignard reagents with electrophiles generally takes place at C-3 to give terminal acetylenic compounds. Reaction with carbon dioxide gives a mixture of acetylenic and allenic acids. These results are consistent with the initial formation of an allenyl Grignard reagent which undergoes a slow prototropic rearrangement to a mixture of acetylenic and allenic Grignard reagents during the time needed to complete the reaction with magnesium. Passage of oxygen through a solution of (9) gave the two hydrocarbons (10) and (11) (2:1) in quantitative yield. (Scheme 6).

Preparation of αα’-dibromoalkynes from alkynediols can be a troublesome reaction but proceeds well with triphenylphosphine dibromide.

Reactions of Acetylenes. — Organoboranes. Interest in the trialkylalkynylborates remained at a high level during 1975. Table 1 below illustrates some of the transformations undergone by these intermediates during the period under review. The vic-diorganoboranes prepared by hydroboration of diphenylacetylene undergo oxidation with chromium trioxide-pyridine to give trans-stilbene. A book on the use of organoboranes in synthesis has been published.

Organoaluminium Compounds. The hydroalumination of alkynes with di-isobutyl-aluminium hydride has been studied and the observations interpreted in terms of mechanisms involving (i) electrophilic attack by R2A1H at the triple bond; (ii) addition of the A1 — H bond in accord with developing pπ–pπ or pπ–pπ polarizations to yield the cis-adduct; (iii) isomerization of the cis-adduct to the trans-adduct where feasible, and (iv) in cases where the corresponding 1-alkyne is formed, the cis-elimination of R2A1E (E = Br, Cl, SEt, or OEt) from the trans-adduct. Alkynylalanes couple with alkyl halides in good yields, but only one of the three alkynyl groups is utilized; the unreacted alkyne can, however, be recovered. The acetylenic acetal (12) is reductively rearranged to the vinyl ether (13) with lithium aluminium hydride. The mechanism (Scheme 7) involves non-regiospecific addition of lithium aluminium hydride/dentericle to the triple bond followed by hydride/deuteride cleavage of the acetal link.

Cycloaddition Reactions of Acetylenes. — Cycloadditions with Dimethyl Acetylene-dicarboxylate (DMAD) and Alkyl Propiolates. Interest in the wide variety of products obtainable from dimethyl acetylenedicarboxylate and ethyl propiolate was at a high level during the past year. Table 2 summarizes the results of many of these studies. Noteworthy examples include 1,5- and 1,11-dipolar cycloadditions, insertion into αω-dodecatrienediylnickel to give 12-and 14-membered rings, and trapping of the intermediate dipolar species by protic solvents to completely alter the reaction pathway.

Other Cycloadditions and Orbital-symmetry Allowed Reactions. Benzyl propargyl ether (14) is known to undergo a facile Claisen rearrangement at 90 °C to 2-indanone. Attempts to extend this reaction to a general synthesis of cyclopentenones using allyl ethynyl ethers have been unsuccessful. Treatment of (15) with sodamide gave (16) and non-nucleophilic bases gave only a polymeric product. The scope of the orthoester Claisen rearrangement has been broadened to give functionalized di- and tri-substituted olefins from ally lie alkynyl alcohols. The predominant isomer is that with the bulkier substituent trans to the ester side-chain (Scheme 8). The base-catalysed rearrangements and cycloadditions of allyl 3-phenylprop-2-ynyl ethers such as (17) leading to tetrahydronaphtho[2,3-c] furans (18) have been rationalized in terms of base-catalysed isomerization of (17) to an allene, a [4 + 2] cycloaddition, and subsequent hydrogen shifts. Metallation of ββ-unsaturated alkynyl ethers can lead to a [2,3]- or [1,2]-sigmatropic rearrangement. The former path leads to allenic alcohols and is particularly favoured at lower temperatures (Scheme 9).

Acetylenic carboxylic acids react with trialkylphosphine-carbon disulphide zwitterions to produce fair yields of the adducts (19). In contrast, methyl propiolate gives 2,6- and 2,7-bis(methoxycarbonyl)tetrathiafulvalene. Following the preparation of the stable cyclobutadiene (20) another such compound has been prepared as shown in Scheme 10. Further extensions of the reactions of keteneimmonium salts for building four-membered rings by [2 + 2] cyclization with acetylenes are shown in selective. Gas-phase pyrolysis of cis- and trans-1,2-diethynylcyclobutane (22) gives 1,2-dihydropentalene (23) and bicyclo[4,2,0]octa-1,5,7-triene. Pyrolysis experiments with the methyl derivatives showed that the bis-allenes (24), formed by a [3,3] sigmatropic rearrangement, are the initial products. Pyrolysis of the diyne (25) gives a 97% yield of the cyclobutene (26). Phenanthra-9,10-quinone undergoes [2+2] cyclo-additions with ynamines and alkyl-substituted alkylthioacetylenes. The addition products with the latter reagents can be easily transformed into hydroxyfuranones and furans.

Additions to the Acetylenic Bond. — Electrophilic Additions. Acylation of alkynes with the cycloalkylfluoroborate (27) gives (28) as the major product. No cyclized product corresponding to (29a) could be isolated. The other products were the anticipated allenic and β-chlorovinyl ketones. The failure to isolate compounds such as (29b) contrasts with results on linear acylium ions and suggests that there is some significant barrier to this cyclization, possibly involving either ring strain or intermediate carbenium ion stabilities. The addition of acyl chloride–aluminium trichloride complexes and of acyl triflates to several acetylenes has been studied and evidence obtained of addition proceeding partly via a vinyl cation intermediate. In the case of aroyl chlorides or triflates the intermediate vinyl cation can be intercepted by the aromatic nucleus to give indenones. The differences in behaviour between the two reagents can be explained by the hardness of the triflate anion as a nucleophile compared to the tetrachloroaluminate anion. The stereochemistry of the products and the full mechanism of the addition have been discussed at length. The optically active Dewar benzene (30) has been synthesized in 33% optical purity using the menthyl ester of (31) as outlined in Scheme 11. Vinyl cations are also intermediates in the zinc bromide-catalysed addition of aralkyl bromides to acetylenes and the relative rates of diphenylmethyl chloride-zinc chloride addition to acetylenes and the corresponding alkenes are similar except for cis- and trans-stilbene.

The acid-catalysed-cyclization of a triple bond in biomimetic type synthesis has been further exemplified by the conversion of (32) into (33) en route to longifolene (34). 20-Ketosteroid type functional groups can be produced from compounds such as (35) and the cyclization can be controlled to produce predominantly trans- or cis-hydrindane systems depending whether carbonium or episulphonium ions are involved. The addition of fluorosulphonic acid to a series of alkynes proceeds instantaneously to give alkenyl fluorosulphonates as the primary reaction products. Terminal alkynes give syn:anti addition in the ratio 4:1, the highest ratio yet observed for protic additions to such systems. The acetylenic bond in (36) is potentially capable of stepwise ionization of both leaving groups to give a bis-annelated product. However, on acid solvolysis entirely monocyclic products were produced showing that (36) provides only one site of unsaturation capable of nucleophilic π-participation. Similar remote triple bond participation has been observed in the solvolysis of 6-octyn-2-en-2-yl trifluoromethane-sulphonate (37).

(Continues…)Excerpted from Aliphatic Chemistry Volume 5 by A. McKillop. Copyright © 1977 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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