Aliphatic Chemistry Volume 4

A Review of the Literature Published During 1974

By A. McKillop

The Royal Society of Chemistry

Copyright © 1976 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-572-0

Contents

Chapter 1 Acetylenes, Alkanes, Allenes, and Olefins By D. W. Dunwell, J. C. Saunders, and B. P. Swann, 1,
Chapter 2 Functional Groups other than Alkanes, Acetylenes, Allenes and Olefins By E. W. Colvin, 81,
Chapter 3 Naturally Occurring Polyolefinic and Polyacetylenic Compounds By G. Pattenden, 205,
Chapter 4 Chemistry of the Prostaglandins By G. Pattenden, 243,
Author Index, 267,

CHAPTER 1

Acetylenes, Alkanes, Allenes, and Olefins

BY D. W. DUNWELL, J. C. SAUNDERS, AND B. P. SWANN

1 Acetylenes

Synthesis of Acetylenes. — Full experimental details have been given for the preparation of alkynes and dialkynes by the reaction of mono- and di-halogenoalkanes with lithium acetylide-ethylenediamine complex. Dimethyl sulphoxide (DMSO) is the preferred solvent for this reaction. Alkylcopper compounds RCu react with copper acetylides to give disubstituted acetylenes, the products of unsymmetrical coupling.

Lithium ethynyl borates, which can be readily prepared from trialkylboranes and lithium acetylide-ethylenediamine complex, are decomposed by iodine to produce the terminal alkylacetylene in high yield. This represents an extension of the previously reported synthesis of internal acetylenes by an analogous procedure (Scheme 1). A similar type of transformation can also be carried out using methanesulphinyl chloride in place of iodine.

Only the strong base combination of sodamide and sodium t-butoxide was found to be capable of producing the required syn-elimination of hydrogen bromide from 1-bromocycloalkenes to give the corresponding cyclo-alkynes.

An ingenious new synthesis of acetylenes starts with bis(tri-n-butylstannyl)-ethylene. Treatment with one equivalent of butyl-lithium converts this compound into the corresponding monolithium derivative, which can then be alkylated and the tri-n-butylstannyl group cleaved with lead tetra-acetate in acetonitrile to give the acetylene (Scheme 2). An advantage in the use of the lithium intermediate is that addition of this compound to a copper acetylide gives an R2CuLi species, the tri-n-butylstannylethenyl group of which can be transferred to an αβ-unsaturated ketone. Oxidation of the resulting vinylstannane derivative with lead tetra-acetate gives the terminal acetylene, and the overall process constitutes a method for the preparation of ethynyl ketones [e.g. (1)] which are not accessible by conjugate addition using dialkynylcopper-lithium species.

Two convenient syntheses of t-butylacetylene from pinacolone have been reported, which involve the use of either phosphorus pentachloride-potassium t-butoxide in DMSO or trifluoromethanesulphonic anhydride in carbon tetrachloride containing pyridine.

Potassium fluoride and tetraethylammonium fluoride are known to be good agents for the promotion of dehydrohalogenation reactions. Good yields of acetylenes are obtained from vinyl halides when the anti configuration is present. The syn-compounds generally give good yields of the corresponding allenes. The reactions are catalysed by crown ethers.

A simple preparative procedure for acetylenic carboxylic acids by alkylation of the lithium salts of acetylenes by ω-bromoalkanoic acids in hexamethyl-phosphortriamide has been described.

The novel vinylcuprate reagent (2) has been found to be a useful three-carbon fragment. A survey of its reactivity with organic halides shows that the reagent is very specific for propargyl and allyl halides. Benzyl bromide is not attacked.

The reaction of 1-bromoalk-1-ynes with two equivalents of butyl-lithium gives 3-butylalk-1-ynes (3) after prolonged treatment. The intermediate is a dilithioalkyne, which can also be prepared directly from terminal alkynes, and which undergoes alkylation at the 3-position.

αβ-Unsaturated ketones react with chlorovinyltriphenylphosphorane to give the corresponding vinyl chloride. Treatment of these compounds with butyl-lithium gives an unsaturated carbene, which rearranges to give the corresponding alkenylacetylene. The reaction of dimethyl phosphonodiazomethane with aldehydes has been extended to include sugars and sugar aldehydes, which are converted into acetylenes containing one more carbon atom.

Trimethylsilylacetylenes are converted into αβ-acetylenic amides on treatment with dialkylcarbamoyl chlorides and aluminium chloride. Use of Castro–Stephens conditions for the coupling of m-iodophenylacetylene-copper(I) salt in pyridine gives a 4.6% yield of the cyclic hexamer.

Cyclo-octatetraene oxide can be converted into enynes by the sequence shown in Scheme 3.

3,3,6,6-Tetramethyl-1-thia-4-cycloheptyne (4), the first isolable cycloheptyne, has been synthesized by lead tetra-acetate oxidation of the corresponding dihydrazone. The large deformation of the C — C [equivalent to] C — C angles causes the 13C [equivalent to] C resonances to shift to lower field, and the reactivity of (4) in addition processes is enhanced. Thus (4) will react with phenyl azide, nitrones, carbon disulphide, and dichloroketen to give the products (5a), (5b), (6a), and (6b), respectively (Scheme 4).

The first synthesis of cyclononyn-5-one involves the fragmentation of the tosylhydrazone (7) with base.

Use of Acetylenes in Synthesis. — Interest in the use of organoborane derivatives of acetylenes as synthetic reagents has continued unabated. The alkynyl-trialkylborates (8), which are prepared by the addition of alkynyl-lithium salts to trialkylboranes, are particularly useful. Protonolysis by acetic acid gives olefins in good yield, and use of the thexylborane derivatives enables good stereospecificity to be maintained. The reaction of (8) with acetyl chloride followed by heating gives the 2-oxa-3-borolens (9), which can be oxidized by the Jones reagent to give αβ-unsaturated ketones. This method has proved to be particularly useful for the preparation of hindered ketones. Similarly, the reaction of chloroalkyl alkyl ethers with (8) gives a mixture of isomers (10) and (11), depending on the solvent and the structure of the borane. Addition of water to the mixture results in selective hydrolysis of (10) to (12). Hydrolysis of the residue with acetic acid converts (11) into (13), and the overall transformation constitutes a stereospecific synthesis of allyl alkyl ethers.

The reaction of (8) with oxirans gives the six-membered cyclic compounds (14). These intermediates can be cleaved with hydrogen peroxide to give γ-hydroxy-ketones (15); protonolysis by acetic acid gives trisubstituted alkenes of the homoallylic alcohol (16) stereospecifically; and the tetrasubstituted derivatives (17) can be obtained by use of a sodium hydroxide–iodine work-up procedure. These transformations are summarized in Scheme 5.

In a similar series of reactions, dialkylboranes can be converted into alcohols and into amines (Scheme 6).

Thexylborane reacts with two equivalents of 1-iodo-alk-1-ynes to give (18). Addition of two mole equivalents of sodium methoxide to (18; R = Bun) gives trans-1,4-di-n-butylbuta-1,2,3-triene. Hydroboration of the product with di-isoamylborane and protonolysis gives pure cis,trans-dodeca.-5,7-diene by addition across the central double bond.

Perhaps the most interesting use of borate salts of acetylenes which has been described has been the functionalization of the 4-position of pyridine. Many derivatives can thus be obtained which are difficult to prepare by other routes (Scheme 7).

Acetylenic acetals can be converted stereoselectively into α-keto-ethers or cis-allylic ethers by treatment with R2BH compounds followed by oxidation or protonolysis.

Addition of alkyl-lithium reagents to allylic alcohols and diphenylacetylenes has been studied previously. Reaction with propargyl alcohols gives good yields of the 2-butyl allyl alcohol. When a methoxy-group is present, elimination occurs and an allenic alcohol is formed, e.g. (19).

Lithio-1-trimethylsilylpropyne reacts with cuprous iodide in ether at -78 °C to give the corresponding organocopper compound, which reacts with ethyl trans-penta-2,4-dienoate to give a 4:1 mixture of allenic and acetylenic products arising by a 1,6 addition across the system. Removal of the silyl group with silver nitrate-sodium cyanide has shown that this process constitutes a simple route to 1,5-enynes and 1,4,5-trienes.

The use of acetylene derivatives in heterocyclic synthesis has been widely exploited. For sulphur-containing heterocycles the addition of thioacetate to diphenylacetylene in DMSO provides a convenient route to tetraphenyl-thiophen. Thiourea adds to penta-1,4-diyn-3-ones to give 2,6-dialkyl-4H-thiapyran-4-ones. Disulphur dichloride adds to ethyl phenylpropiolate to give a product which, on oxidation with hydrogen peroxide, undergoes cyclization to give the benzothiophen 1,1-dioxide (20).

Irradiation of 4-oxo-2,6-diphenyl-4H-thiapyran 1,1-dioxide in the presence of phenylalkynes gives moderate yields of thiepin 1,1-dioxides (21).

Diels–Alder addition of ynamines to pyrimidines followed by a retro elimination of a nitrile moiety constitutes a method for the preparation of substituted pyridines, and rules have been established for prediction of the orientation of substituents in the products. Nucleophilic addition of hydrazines to penta-1, 4-diyn-3-ones gives pyrazoles. A similar type of reaction between o-phenyl-enediamine and diarylprop-1-yn-3-ones gives benzodiazepines. Methyl propiolate reacts with enamines of β-keto-esters to give trans-dienamino-esters (22). Deuteriation experiments show that a 1,5-hydrogen shift occurs in this step. The products can be further transformed into 2-pyridones (Scheme 8).

Propiolic acid dianion has been used as a nucleophilic acyl synthon in the total synthesis of ( ±)-pestalotin.

Ynamines are acylated by diketen and the intermediates thus formed can be cyclized to derivatives of 2-amino-4-pyrone. Irradiation of non-cisoid 1,2-dioxo-compounds with 1-alkylthioprop-1-ynes in benzene gives cis- and trans-2-alkylthiobut-2-ene-1,4-diones via an oxeten intermediate. The cis-compound can be ring-closed to a furan derivative with stannic chloride. Acid-catalysed ring closure of 1,1-diphenylhepta-2,4-diyne-1,7-diol gives the 2,3-dihydro-y-pyrone (23) in good yield. Base-catalysed cyclization of the acetylenic allyl alcohol (24) yields the alkenyl furan (25). Dicyanoacetylene forms 1:1 adducts with THF and diethyl ether, such as (26), without either u.v. irradiation or addition of a radical initiator.

The Mannich reaction is often used for aminomethylation of terminal acetylenes, but reaction conditions vary for different amines. A general method has now been described which gives good yields with various amines.

Cycloaddition Reactions of Acetylenes. — Cycloadditions with Dimethyl Acetylenedicarboxylate. Table 1 summarizes some of the cycloaddition reactions undergone by dimethyl acetylenedicarboxylate (DMAD).

Other Cycloaddition and Orbital-symmetry-allowed Reactions. Phenyl trifluoromethanesulphonyl acetylene undergoes extremely facile Diels–Alder reactions with dienes, and has generally been found to be more reactive than dimethyl acetylenedicarboxylate (DMAD). Cycloaddition of symmetrical acetylenes to hexa-1,2,4,5-tetraene provides a new and convenient route for the preparation of [2,2]paracyclophanes (27).

Dicyanoacetylene reacts with steroidal systems such as ergosteryl acetate to give products of both Diels-Alder addition and an ‘ene’ reaction.

2,5-Dimethoxycarbonyl-3,4-diphenylcyclopentadienone reacts with acetylenes to give arenes.

Electron-deficient thiophens such as (28) undergo a [2+2] cycloaddition with ynamines to give (29). A high yield of the bicyclo-enamine (30), which has three asymmetric centres, has been achieved by ynamine addition to 5-methyl-2-cyclohexenone. The addition of 1-diethylaminopropyne to the sydnone species (31) is postulated to involve the hitherto unknown acyclic valence tautomer (31a).

The reaction of ethyl propiolate with N-formyl-L-proline in acetic acid has been presumed to proceed via the intermediate 1,3-dipole (32). Further examples of 1,3-dipolar additions to acetylenes include the reaction of nitrile oxides with silylacetylenes and of phenyl azide with 1,1,4,4-tetra-ethoxybut-2-yne. Diazocyclopentadienes add to acetylenes to give diaza[4,4] spirenes, which undergo 1,5-sigmatropic shifts to give aza-indolines (33) or indazoles (34). Photolysis of the precursors also gives rise to the (1+2) cycloadducts such as (35).

Condensed thiophens are obtained via consecutive [2,3] and [3,3] sigmatropic rearrangements when arylprop-2-ynyl sulphoxides are heated in suitable protic solvents (Scheme 9). An analogous type of reaction utilizes the addition of di(methoxycarbonyl)carbene to the phenyl propargyl sulphide (36) followed by a [2,3] sigmatropic rearrangement to the allene (37).

Thermolysis of homoallyl ethers proceeds in a concerted manner via an eight-centred transition state and follows a first-order rate law. The thermal rearrangement of 7-propargyloxycycloheptatriene gives a mixture of bicyclo-[3,3,2]deca-3,7,9-trien-2-one (38) and the unstable 2,7-dihydrocyclohepta-[6]pyran (39). The major photoproduct of 6-phenylhex-2-yne is the bicyclo-[6,3,0]undeca-1,3,5,7-tetraene (40), which is derived from the phenyl singlet excited state. Thermal cyclization of meta-substituted-phenyl propargyl ethers yields a mixture of 5- and 7-substituted chromenes, and the factors which affect the product ratio have been investigated.

Other Additions to the Acetylenic Bond. — Electrophilic Additions. Studies of the initial reaction rate and product composition for the reaction of various acetylenes with hydrogen chloride give results which are consistent with reaction via competing AdE2 and anti Ad3 reaction mechanisms. In a related study of the electrophilic addition of hydrogen chloride to phenyl [2-2H]acetylene it was claimed that considerable participation by the forbidden syn [2π + 2σ] addition process occurred. Kinetic studies of the electrophilic addition of 2,4-dinitrobenzenesulphenyl chloride with 1-phenylpropyne suggest that the episulphonium ion species (41) is an intermediate in the process.

Although phenylacetylene polymerizes on treatment with xenon difluoride, alkylacetylenes react with the same reagent to give good yields of the tetrafluoro-adducts, and the process is catalysed by hydrogen fluoride. Addition of BrCl and IC1 to ethyl but-3-ynoate gives (42), but addition of sulphenyl halides results in the opposite orientation pattern and leads to (43). Different mechanisms operate in each case, and these have been evaluated both by orientation and kinetic studies. Phenylsulphenyl chloride reacts by an AdE2 mechanism whereas ICl addition involves a combination of AdE3 and AdE4 mechanisms. The addition of phenylselenyl trifluoroacetate to acetylenes proceeds as expected, and hydrolysis of the trifluoroacetate moiety generates the corresponding ketone (Scheme 10). Likewise, the addition of sulphonyl bromides RSO2Br to acetylenes gives a mixture of cis- and trans-adducts in the presence of copper(II) bromide. In contrast, pure thermal addition gives only the trans-isomer (44). Both isomers readily lose hydrogen bromide on treatment with base and give the acetylenic sulphone.

Although vinyl cations are well-documented intermediates in the addition reactions of acetylenes, they have not been physically characterized to date. In trifluoroacetic acid solution ethynylferrocenes (45) bearing a 2-t-butyl substituent undergo protonation to give the corresponding vinyl cations. Although these are short-lived, they can be observed in this case by 1H n.m.r. spectroscopy as a result of the stabilizing effect of the orbitals on the Fe atom.

But-2-yne reacts with isobutyryl fluoroborate in methylene chloride-tetrachloroethane to give 2,3,5-trimethylcyclopent-2-enone as the major product, probably via a vinyl cation intermediate (Scheme 11).

Nucleophilic Additions. Tetrahydropyran-2-thiol adds to acetylenes and olefins in the presence of base to give protected thiol derivatives in good yield. The thiol grouping can be liberated using silver nitrate followed by chloroform-HCl treatment. There was no evidence to show that these compounds existed in the tautomeric thioketone form (Scheme 12).

Hydroxylamines add to toluene-p-sulphonylacetylenes by attack either via nitrogen or via oxygen, depending on the structure of the acetylene (Scheme 13). The kinetics of the hydration of ynamines have been investigated in water-dioxan by stopped-flow spectrophotometry. The very useful addition of di-isobutylaluminium hydride to acetylenes to give cis-alanes has been studied kinetically, and the role of molecular association of the reagent investigated. The reaction of the cis-alanes obtained by this procedure with allyl bromides in the presence of copper(I) chloride via a coupling reaction constitutes a stereoselective synthesis of trans-1,4-dienes (Scheme 14). The lithium aluminium hydride reduction of alk-1-yn-3-ols has been shown to proceed via a site-specific hydride transfer to C-2. The mechanism proposed (Scheme 15) rationalizes the observed reciprocal relationships between solvent basicity and the extent of cis-reduction for these systems. Reduction of such systems where an alkoxy function is attached to the carbon atom adjacent to the triple bond leads to α-allenic alcohols instead. A further example of this reaction is the reduction of the hydroxymethylacetylene (46) to the trans-olefin (47) with lithium tri-t-butoxyaluminium hydride.

(Continues…)Excerpted from Aliphatic Chemistry Volume 4 by A. McKillop. Copyright © 1976 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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