Aliphatic Chemistry Volume 2

A Review of the Literature Published during 1972

By W. Parker

The Royal Society of Chemistry

Copyright © 1974 The Chemical Society
All rights reserved.
ISBN: 978-0-85186-512-6

Contents

Chapter 1 Acetylenes, Alkanes, Allenes, and Alkenes By R. S. Atkinson, 3,
Chapter 2 Functional Groups other than Acetylenes, Alkanes, Allenes and Olefins By E. W. Colvin, 128,
Chapter 3 Naturally Occurring Polyolefinic and Polyacetylenic Compounds By G. Pattenden, 213,
Chapter 4 Chemistry of the Prostaglandins By G. Pattenden, 258,
Author Index, 309,

CHAPTER 1

Acetylenes, Alkanes, Alienes, and Alkenes

BY R. S. ATKINSON

1 Acetylenes

Reviews. — Recent reviews on areas of acetylenic chemistry include synthetic routes to average-ring-size cycloalkynes, a study of the bonding in metal-acetylene complexes, transition-metal complexes of acetylene, intra-molecular cyclization reactions with acetylenic bond participation, oligomerization of acetylenes induced by metals of the nickel triad, an article on the handling of acetylenic compounds, and a book on preparative acetylenic chemistry.

Synthesis. — Numerous examples have appeared illustrating the potential of the method for synthesizing acetylenic carbonyl compounds by thermolysis of hydrazones derived from α, β-epoxy-ketones and certain 1-aminoaziridines. As an example, (1) is converted via (2) into the acetylenic aldehyde (3).

Although Michael addition of acetylenic anions to conjugated enones failed, γδ-acetylenic ketones, e.g. (4), were obtained in fair to good yield by addition of alkynylalanes (5). The organoalane is prepared from the lithium salt of the terminal acetylene and dialkylaluminium chloride. A plausible pathway for the reaction involves intramolecular delivery of the alkynyl group through prior complexation with the carbonyl oxygen (6).

Triacetylenic boranes are derived from lithium acetylides and boron trifluoride etherate in THF at – 20 °C. They react with ethyl diazoacetate to give homologated propargyl esters (7) after hydrolysis. Hydration of these βγ-acetylenic esters using mercuric ion is regiospecific: only γ-keto-esters (8) are produced and no β-keto-esters. One possibility is that carbonyl oxygen participation is directing the hydration, as in (9).

Transformation of aldehydes into homologated acetylenes is carried out via the dibromo-olefin (10). Furthermore, the lithium acetylides (11) may be treated with carbon halides, aldehydes, ketones, epoxides, or carbon dioxide to give derivatized acetylenes.

β-Keto-esters (12) are converted in good yield into 2-alkynoic esters (13) by oxidation of their pyrazolones with thallium(m) nitrate. The procedure is claimed to be simpler than the method previously used for this transformation, which involves chlorination and alkali treatment of pyrazolones.

Standard oxidative coupling methods for acetylenes use the Glaser method (CuCl, NH4C1, aqueous alcohol, O2) or Eglinton and Galbraith’s method [Cu(OAc)2, pyridine, alcohol]. The former reaction can be accelerated by addition of NNN’N’-tetramethylethylenediamine and the yield improved by using dimethoxyethane as solvent.

The triethylsilyl group has found extensive use in poly-yne synthesis. Thus the bromoalkyne (14) is coupled to phenylacetylene (Cadiot-Chodkiewicz reaction) and the diyne (15) is liberated quantitatively on treatment with base. An extension of this procedure involves (a) oxidatively coupling protected terminal alkynes, (6) partially desilylating (monitoring by u.v.) and separating, (c) recoupling, and (d) completely desilylating [(16) [right arrow] (17)]. In addition the reagents Et3Si(C [equivalent to] C)mH (m = 1, 2, or 4) may be used in excess as one component in mixed oxidative couplings, extending an acetylene by up to four yne units in a single step after removal of the triethylsilyl group with base.

Arylacetylenes (18) are available by coupling of arylcopper reagents with iodoethynyl(trimethyl)silane (available in high yield from ICI + Me3SiC [equivalent to] CSiMe3), the protecting group being readily detached with alkali. This route is complementary to the Stephens-Castro coupling between an aryl iodide and a suitably protected cuprous acetylide, CuC [equivalent to] CR.

Aromatic iodine, e.g. (19), may be exchanged for acetylenes using CuIsalts in the presence of potassium carbonate. The method avoids the requirement of dry cuprous acetylides.

5,5-Disubstituted 3-nitroso-2-oxazolidones (20) are transformed by butylamine in ether into acetylenes; 2-ethynylthiophen, 3,5-di-t-butylphenylacetylene, and dicyclopropylacetylene have been prepared in this way.

Stepwise addition of sulphur and cyanide to acetylides provides 1-alkynyl thiocyanates (21); they may be used for introduction of an RC [equivalent to] C — S — unit, as in the preparation of the previously unknown NN-dialkylalk-1-ynesulphenamides (22).

Ring-opening of the epoxide (23) takes place on heating with (S)-(—) -3-t-butyloxyoct-1-ynyldimethylalane (24) in toluene. This reaction is employed in a prostaglandin synthesis which introduces the functionalized eight-carbon side-chain in optically active form. The desired ring-opening at C-12 (prostaglandin numbering) is dependent on preliminary covalent bond formation between the aluminium and the side-chain oxygen with subsequent intra-molecular delivery of the alkyne, as in (25).

A route to acylacetylenes uses α-diazo-β-hydroxy-ketones (or -esters) (26). These are readily accessible by condensation of aldehydes with acyldiazomethanes and yield acetylenes on treatment with boron trifluoride.

Ynamines (27) are formed in the reaction of di-iminium salts (28) with t-butoxide anion or triethylamine.

Directed attack on the propargyl anion occurs when the dilithium salt of the 2-propargylthiothiazoline (29) is alkylated. The phenylpropargylated product (30) is reduced with zinc dust and acetic acid to give the diacetylene (31) and the allenylacetylene (32) in a ratio of 1:8.

Acetylenes are often found as components of synthesized macrocyclic systems, chiefly as a result of the ease of linking two C [equivalent to] C units by methods referred to earlier. Among annulenes which have been prepared by this method are (33), (34), and (35), the latter containing the substituent R within the cavity of the π-electron cloud. Annulenones, e.g. (36), (37), and (38), are prepared similarly, as are [m,n]paracyclophadiynes (39); comparison of the electronic spectra of these latter compounds with those of the analogous cyclic diacetylenes (40) indicates transannular π-electronic interaction in the cases (m = n = 3) and (m =3, n – 4).

Various diacetylenes have been constructed to examine enforced intra-molecular interaction between triple bonds. Synthesis of the diacetylene (41) has been accomplished by cupric chloride coupling of 2,2′-dilithiodiphenyl-acetylene. The close proximity of the triple bonds in (41) results in the formation of (42) on treatment with hydrogen bromide. No evidence was forthcoming for an intermediate tetrahedrane (43) in reactions of (41) and its derivatives. A similar interaction is revealed in the reaction of (44) with hydrogen bromide, where (45) is obtained. Alkylation of the derived dilithium diacetylide of (44) with the appropriate alkyl di-iodide gave (46) . The ring inversion barrier for (46; n = 2) was measured (n.m.r.) and found to be 75 kJ mol-1; an X-ray structure determination of this compound has been reported, together with that of l,8-bis(propyn-T-yl)naphthalene.

Other acetylenes prepared include a-ethynylamines (47) from the corresponding alcohols; acetylenic ethers or tertiary amines (48) by reaction of lithium salts (49) with aldehydes in the presence of zinc iodide; acetylenic amino-alcohols, e.g. (50), from acetylenic Grignard reagents and α-(dialkylamino)tetrahydropyrans ; chlorocyanoacetylene from acrylonitrile and chlorine; various acetylenes by elimination of hydrogen bromide from 1,2-dibromides with NaNH2-ButONa in aprotic media; dichloroacetylene from trichloroethylene in the presence of epoxides ; long-chain diynoic and triynoic acids; and acetylenic derivatives of selenophen. Convenient procedures for the synthesis of cyclononyne and cyclonon-1-en-5-yne (51) from the readily available bromocycloalkenols (52) and (53) have been reported.

Use of Acetylenes in Synthesis. — Reactions involving Metals. The thiacyclo-heptyne (54) has been converted into an isolable cyclobutadiene-containing dimer [(55a) or (55b)] via the yellow palladium complex (56). A distinction between (55a) and (55b) and the extent of bond delocalization for this cyclobutadiene have yet to be established; it reacts avidly with dimethyl acetylene-dicarboxylate and oxygen.

Cuprate species, formally R2Cu-, resulting from cuprous halide and two equivalents of an organolithium, are useful for conjugate addition to C=C — C=O and C [equivalent to] C — C=O systems. A disadvantage in the reaction is that only one of the groups R is utilized. By employing the mixed cuprate {Me(CH2)2C[equivalent to]C}R Cu, this waste can be avoided, the group R being preferentially transferred. Thus preparation of the mixed cuprate (57) and reaction with cyclohexenone gave (58) in > 95 % yield.

Diacetylenes are cyclotrimerized to the unsymmetrical isomer (59) in high yield using Ni(CO)2 (PPh3)2. Previous catalysts for this transformation gave low yields of symmetrical and unsymmetrical isomers. This catalyst also cyclo-cotrimerizes acetylenes with olefins; N-methylmaleimide and phenylacetylene give the 2:1 adduct (60) and the 2:2 adduct (61).

Hydroformylation of alkynes catalysed by rhodium normally proceeds reluctantly and in poor yields. However, hydroformylation of but-1- and -2-ynes to n-pentanal and 2-methylbutanal is greatly improved using a specific excess of triphenylphosphine.

Conversion of acetylenes into substituted maleate esters (62) by addition of two carboxy-groups to the unsaturated system is achieved using palladium and mercury salts in the presence of carbon monoxide. Diphenylacetylene and aromatic nitro-derivatives in the presence of carbon monoxide and Rh6 (CO)16 combine to yield maleimides (63), the carbon monoxide functioning as reducing and carbonylating agent.

Stereospecific synthesis of cis-disubstituted or trisubstituted olefins from mono- or di-substituted alkynes can be accomplished via hydroboration to dialkylvinylboranes followed by addition of sodium hydroxide and iodine. By treatment of the vinylborane with cyanogen bromide in methylene chloride solution, the complementary procedure, namely conversion into the trans- olefin, may be effected. In the cis-producing case, the stereochemistry is believed to be the result of trans-elimination of iodide and boron from the intermediate (64). In the corresponding intermediate (65) produced using cyanogen bromide, the strongly electron-withdrawing character of the cyanide enhances cis-elimination with formation of the trans-olefin (Scheme 1).

Details are given for the conversion of methyl and ethyl 2-alkynoates via monohydroboration into (a) cis-αβ-unsaturated esters by protonolysis or (b) α-keto-esters by controlled oxidation with H2O2.

1,3,2-Benzodioxaborole (66) is readily available by the reaction of catechol with borane. It adds to alkynes to give 2-alkenyl-1,3,2-benzodioxaboroles (67) with stereospecificity and regioselectivity operating as usual, placing the boron in the less sterically hindered environment. The latter are protonolysed to the m-olefin (68), hydrolysed to the alkeneboronic acids (69), or oxidized to ketones (aldehydes) (70). Compound (67) is also converted into alkenyl -mercuric chlorides (71) on treatment with mercuric acetate with retention of configuration.

Reaction of amines and diarylbutadiynes in the presence of small quantities of cuprous chloride is a known route to pyrroles. Omission of the cuprous chloride results in the pyridine (72).

Hydrosilylation of terminal acetylenes using Ziegler-type catalysts results in an (unexpected) linear dimerization to give (73) and (74).

Oxidative addition of alkyl halides to vinylrhodium(i) complexes gives isolable alkylvinylrhodium(III ) species (75). Heating the latter gives a trisubstituted olefin whose stereochemistry can be controlled by judicious choice of conditions. Derivation of (76) by addition of rhodium hydride to the acetylene results in an overall conversion of an acetylene into a trisubstituted olefin (Scheme 2).

Diethyl bromomalonates (77) and phenylacetylene in the presence of zinc yield the substituted cinnamic esters (78) if tautomerism is possible (R = H); otherwise the butenoic esters (79) are obtained.

The versatile thallium(m) nitrate (TTN) oxidizes acetylenes to different types of product, depending on the acetylene. Terminal acetylenes are converted into the carboxylic acid with the loss of a carbon atom, diaryl-acetylenes give benzils, dialkylacetylenes give acyloins, and alkylarylacetylenes are oxidized in methanol to alkylaryl acetates (Scheme 3).

Other Syntheses using Acetylenes. a-(Alkylideniminoxy)-ketones (80) are obtained by addition of strong electrophiles to alkynes in nitromethane solution by a mechanism which is presumed to involve a (2,3)-sigmatropic rearrangement of the first formed intermediate (81). Using acyl cations, e.g. (X = MeCO+), an additional product is the β-diketone (82), which is the only product in the case of monosubstituted alkynes.

The propargylic alcohol (83) has been cleverly isomerized to the αβ -unsaturated aldehyde (84) by equilibrating its tetrahydropyranyl ether with the corresponding allenyl derivative in the presence of strong base. After selective hydrolysis of the allenyl acetal (vinyl ether) (85), (84) is easily separable from unchanged (86) by distillation.

The diacetylenic amine (87) gives the piperidone (88) by treatment with dimethylamine, or the pyrrolenine (89) by hydration-cyclization.

Silver carbonate on celite (Fetizon’s reagent) quantitatively converts steroidal 17-ethynyl alcohols, e.g. (90), or cyanohydrins, e.g. (91), into the corresponding ketones (92) at the same rate at which allylic hydroxy-groups are oxidized.

Unsaturated acid chlorides (93) react with monosubstituted alkynes to give mixtures of compounds from which 4-alkylidenecyclopentenones (94) can be separated, which are otherwise not readily accessible.

Attempted déméthylation of (95) and (96) results in cyclization to (97) and (98), respectively.

The following syntheses using acetylenes have also been studied: non-stereospecific formation of halogenoalkenes by addition of titanium halides to alkynes; formation of substituted phenols by addition of ketones to alkynones; addition of aromatic 1,2-diamines or 2-aminomercaptobenzenes to alkynones to give 1,5-benzodiazepines or 1,5-benzothiazepinesl and cyclization of substituted 1,3-alkenynes with thiourea to give pyrimidine thiols.

Cycloaddition Reactions. — Acetylenes undergo many types of cycloaddition reaction and provide valuable starting materials for the synthesis of carbo- and hetero-cyclic systems. Many acetylenes are dipolarophiles, and dimethyl acetylenedicarboxylate (DMAD), because of its ready availability, often plays this role in the formation of a variety of heterocycles. Mesoionic systems often function as the 1,3-dipoles, as in the formation of pyrrole (99) from the Δ2-oxazolium-5-olates (munchnones) (100) and DMAD. The procedure can be extended to fuse pyrrole rings on to the piperidine rings of (101) and (102) in moderate yields. Further examples of 1,3-, 1,4-, 1,5-, and 1,11-dipolar additions to acetylenes are summarized in the reactions shown below.

In the reaction of DMAD with the quinazoline oxide (103), the major products are the stilbene derivative (104) and the benzodiazepine (105). The skeletal rearrangement in Scheme 4 was suggested to account for their formation.

Dibenzoylfuroxan (106) and phenylacetylene on heating in xylene gave the isoxazole (107). The normally suppressed 1,3-dipolar reactivity of furoxans may be enhanced in this case by the C-acyl substituent.

Among [4 + 2] cycloadditions of acetylenes is addition of (108) to the diazanorcaradienes (109) to yield cycloheptatriene derivatives (110); diazanorcaradienes are available by addition of cyclopropenes to 1,2,4,5-tetra-zines.

Many thiophens are surprisingly reactive towards dicyanoacetylene in the Diels–Alder reaction. Since the adducts irreversibly lose sulphur and the starting thiophens are usually readily available (in contrast to the corresponding butadienes or cyclopentadienones), this constitutes a useful route to phthalonitriles (111) and their derivatives.TheDiels-Alder reaction between pyridazinecarboxylic acid esters and 1-diethylaminopropyne is one with an inverse of the normal electron demand; the nature of the product (112) or (113) depends on the ester location in the pyridazine.” The addition of monosubstituted acetylenes to tetrazines as a route to substituted pyridazines has been examined.

Among the more recondite dienes which have been coupled with acetylenes in the Diels–Alder is the rhodium complex (114), formed by addition of Rh(PPh3)3Cl to diyne (115). A similar reaction occurs with the diene (116). Conversion of these rhodium species into cyclopentadienones (with carbon monoxide) or into substituted furans, thiophens, or selenophens (with oxygen, sulphur, or selenium, respectively) can be effected.

An X-ray structure determination of the crystalline product from the silacyclopentadiene (117) and diphenylacetylene shows that this is not the Diels–Alder adduct (118) but a 1:1 crystal complex.

Intramolecular Diels–Alder reaction of the cinnamyl phenylpropiolates (119) continues to be exploited as a method for synthesis of naturally occurring phenolic cyclolignan lactones (120).

(Continues…)Excerpted from Aliphatic Chemistry Volume 2 by W. Parker. Copyright © 1974 The Chemical Society. Excerpted by permission of The Royal Society of Chemistry.
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