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Treatment of the azido(2-heteroaryl)methanones 1–5 with methyl (E)-3-pyrrolidinoprop-2-enoate at room temperature yielded the methyl 1,2,3-triazolecarboxylate 6 and (2-heteroaryl) (pyrrolidino)methanones 1a–5avia an unusual 1,3-cycloaddition reaction. Analogous reactions of the azidomethanones 1 and 2 with the dipolarophiles methyl crotonate, methyl propiolate or methyl but-2-ynoate failed. In contrast, the strained 5-methylenebicyclo[2.2.1]hept-2-ene reacted smoothly with the carbonyl azides 1–5 to give triazoline adducts which subsequently formed the (2-heteroaryl)(6-methylene-3-azatricyclo[3.2.1.0]octan-3-yl)methanones 1b–5b by loss of molecular nitrogen.

4,5-Diphenyl-1,2,3-selenadiazole and 3,5-diphenyl-1,2,4-selenadiazole were alkylated with trimethylsilylmethyl trifluoromethanesulfonate. Quaternisations occurred at N-3 and N-2 respectively. The salts were desilylated to generate transient selenadiazoliumylmethanide (ylide) intermediates. 4,5-Diphenyl-1,2,3-selenadiazol-3-ium-3-ylmethanide, 3, was trapped with dimethyl acetylenedicarboxylate and methyl propiolate in a cycloaddition–rearrangement reaction which gave the pyrazolylvinyl vinyl selenides 6 and 7. 3,5-Diphenyl-1,2,4-selenadiazol-2-ium-2-ylmethanide, 10, ring-expanded in situ to 4,6-diphenyl-2H-1,3,5-selenadiazine, 13.

Stereocontrolled syntheses of the 14α,17α-propano and 14β,17β-propano analogues of estradiol are described, together with those of numerous derivatives in which additional functionality is incorporated into the bridged system. Intramolecular aldol condensation of 17β-acetoxy-3-methoxy-20-oxo-19-nor-17α -pregna-1,3,5(10)-triene-14-carbaldehyde 1 furnishes 3-methoxy-171-oxo-14,17α-prop-172 -enoestra-1,3,5(10)-trien-17β-yl acetate 2, which is transformed into 14,17α-propanoestra-1,3,5(10)-triene-3,17β-diol 17. In the first of two synthetic approaches to the 14β,17β-propano series, cycloaddition of methyl propiolate to 3-methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate 25 gives a 14,17-bridged intermediate 26, in which the latent propyne equivalency of the dienophile is elaborated through selective functional group transformations to give 17-acetoxy-3-methoxy-20-oxo-19-nor-14β -pregna-1,3,5(10)-triene-14-carbaldehyde 50 and the derived product 52 of intramolecular aldol condensation. The second approach entails regioselective functionalisation of 14-allyl-3-methoxy-14β-estra-1,3,5(10)-trien-17-one 54 at C-2′ or C-3′ to give intermediates for intramolecular closure between the chain terminus and C-17, leading to 14,17β-propano-14β-estra-1,3,5(10)-triene-3,17α-diol 64. The results of competitive binding assays of the hormone analogues 17 and 64 toward the estradiol receptor are reported, and compared with those of bridge-functionalised derivatives.

The endocyclic linearly conjugated dienolates from substituted cyclohex-2-enones react with but-3-en-2-one, substituted methyl propenoates, but-3-yn-2-one and methyl propiolate to afford bicyclo[2.2.2]-oct-2-en-1-ols 10a–c, 14a–c and bicyclo[2.2.2]octa-2,5-dien-1-ols 15a,b. The AlCl3-catalysed reaction of 3,5,5-trimethyl-1-(trimethylsiloxy)cyclohexa-1,3-diene 3 with (E)-4-acetoxy- and (E)-4-methoxy-but-3-en-2-one provides trans-8-acetoxy-7-acetyl-3,5,5-trimethyl-1-(trimethylsiloxy)bicyclo[2.2.2]oct-2-enes 22, 23 and trans-7-acetyl-8-methoxy-3,5,5-trimethyl-1-(trimethylsiloxy)bicyclo[2.2.2]oct-2-enes 24, 25. Starting from these bicyclo[2.2.2]octenes, the C13 degradation products of carotenoids including 3-oxo-α-ionone 20, blumenol-C 27 and 1,3,7,7-tetramethyl-2-oxabicyclo[4.4.0]decan-9-one 29 have been synthesized.

[2 + 2]Cycloaddition of the 1,1-dimethoxyalkenes 1 to acetylenic esters, such as dimethyl acetylenedicarboxylate 2a and methyl propiolate 2b, occurs via 1,4-dipolar intermediates which, trapped by methyl propiolate and tert-butyl alcohol, give functionalized 3,3-dimethoxycyclobutenes 3, synthetic precursors to naturally occurring products and biologically active compounds.

An efficient one-pot, three-component process for the preparation of 2-pyridones from a carbonyl compound, ammonia, and methyl propiolate has been found which provides ready access to a key intermediate in the synthesis of huperzine A.

The reaction of methyl (2-pyridyl)acetate with methyl propiolate gave quinolizine derivatives; (2-pyridyl)acetone and 1-(2-pyridyl)butan-2-one reacted similarly. 2-Acetylpyridine and ethyl pyridine-2-carboxylate reacted with methyl propiolate to yield pyrrolo[2,1,5-cd]indolizines. The structures of the products were deduced mainly from their u.v. and n.m.r. spectra.

[1-Alkylpyridin-4(1H)-ylidene] acetates and related compounds react at the exocyclic double bond with electrophilic acetylenes to give 1 : 1 and 1 : 2 adducts by simple Michael addition followed by proton shift. With tetracyanoethylene a related product was isolated and also a compound in which the ester group had been lost. Methyl [1-alkylpyridin-2(1H)-ylidene] acetates give analogous products with methyl propiolate, but-3-yn-2-one, and 4-phenylbut-3-yn-2-one.

The synthesis of 1,4-dihydropyridines unsubstituted in the 1-, 2-, and 6-positions from methyl propiolate, aromatic aldehydes, and ammonium acetate in acetic acid is described. The products were oxidised to the corresponding pyridines. Certain features of their n.m.r. spectra are discussed.

Short syntheses of the natural dibenzofuran, ruscodibenzofuran (1) from readily available phenols are described. The key steps involve initial formation of a 2-isopropenylbenzofuran by reaction of an ortho-halogenophenol with cuprous isopropenylacetylide followed by cycloaddition of methyl propiolate, to provide a functionalized dibenzofuran.

Reactions of methyl propiolate with benzimidazole and its 2-alkyl and aryl derivatives, in acetonitrile, gave the corresponding methyl 3-trans-(benzimidazol-1-yl)acrylates, whereas a reaction with benzimidazole in methanol gave the cis-isomer exclusively. Similar acrylates were formed from methyl tetrolate and methyl phenylpropiolate. Other products were pyrrolo[1,2-a]quinoxalines and a pyrrolo[1,2-a]benzimidazole.

Benzimidazole-2-acetonitrile, ethyl benzimidazole-2-acetate, and their 1-methyl derivatives were heated with methyl propiolate and with dimethyl acetylenedicarboxylate in acetonitrile. The resulting mixtures, on chromatography gave pyrrolo-, pyrido-, and azepino-[1,2-a]benzimidazoles, the structures of which were deduced from their spectral properties.