3- Chloro-3-methylbut-l-yne

Although the isomeric chromenes (48) and (49) obtained from the isoflavanone (47) and 3-chloro-3-methylbut-l-yne could not be separated by chromatography, a chemical separation was achieved. Ring contraction of the 7-methoxy isomer (49) to the benzofuran (50) occurred on reaction with thallium(III) nitrate in methanol the 5-methoxy compound was unaffected. The resulting mixture was readily separated <8iG2li). 

The alkyne is formally derived by a 1,4-dehydrochlorination with ring opening, although subsequent work has shown that the cyclopropene ring-opens even at ambient temperature to 3-chloro-3-methylbut-l-yne and so a 1,2-dehydrochlorination of this is an alternative. The carbene could be formed by several routes from the cyclopropene, and an early experiment with a 14C-labelled compound indicated that the label at C-l of the cyclopropane became C-l of the carbene ... 

Hydroxynoracronycine (40) is a constituent of Atalantia ceylonica and a metabolite of the antitumour compound acronycine its synthesis has been reported (Scheme 6).31 The reaction of l,3-dihydroxy-5-methoxy-9-acridone (36) with 3-chloro-3-methylbut-l-yne and cyclization in situ of the products furnished the chromenes (38) and (39) the formation of the intermediate (37) involves C-alkylation with the chlorobutyne, a reaction encountered previously during the synthesis of flindersine.32 Chromene (39) was converted into 11-hydroxy-noracronycine by successive methylation and demethylation. 

Lewis and his co-workers have reported three interrelated syntheses of acronycine 208 (81T209). In one synthesis, 2,6-dimethoxy-4-hydroxy-2 -nitrobenzophenone 250, obtained as a minor product from Friedel-Crafts acylation of 3,5-dimethoxyphenol with 2-nitrobenzoylchloride, was treated with 3-chloro-3-methylbut-l-yne under basic conditions. The resultant nitro compound 251 was reduced to the amine 252 with zinc. Upon reaction with sodium hydride in DMSO, this amine provided a mixture of de-N-methylisoacronycine 253 and de-N-methylacronycine 210. T>e-N-methylacronycine 210 was converted to acronycine 208 by methylation with methyl iodide (Scheme 42). 

The coupling of 2,3-dihydroxy-10-methylacridin-9(10//)-one 276 with 3-chloro-3-methylbut-l-yne afforded a pyrano[3,2-a]acridine 277 (Scheme 48) (83MI1). 

Reisch et al. (93JHC981) described two different methods for the synthesis of 4-azaacronycine 71. One method involves the fusion of 1,3-dihydroxy-10-methyl-9(10//)-acridone 69 with 3-amino-3-methylbut-l-yne in the presence of CuCb in a closed ampule, followed by methylation (Scheme 13). The second method involves the A-alkylation of 3-amino-l-methoxy-lO-methyl-9(107/)-acridone 70 with 3-chloro-3-methylbut-l-yne, followed by in situ cyclization (Scheme 13). 

Precocene II (125) and other chromenes have been synthesized and screened for their effect on the cloth moth. Precocene II has larvicidal properties. A trifluoro-compound (126), related to precocene, has been synthesized from 3,4-dimethoxyphenol, trifluoroacetone, and allylmagnesium bromide. Several natural chromenes, for example 6-acetyl-2,2-dimethyl-5-hydroxy-8-methoxy-2//-chromene, have been synthesized from the appropriate substituted 2-hydroxyacetophenone and either 2-methylbut-3-en-2-ol or 3-chloro-3-methylbut-l-yne. 2//-Chromenes are rarely prepared from chromanones, but a direct conversion of substituted 2,2-dimethylchromanones, e.g. (127), in high yield, into 2H-chromenes, e.g. (128), has been achieved by the action of PCls. °... 

Dimethylvinylidene carbene generated from 3-chloro-3-methylbut-l-yne using aqueous KOH and a phase-transfer catalyst, has been added to cis,cis-cyclo-octa-l,5-diene to give the mono-adduct. ... 

The compound of formula (4) is coupled with isoprene chloroacetate (1-acetoxy-4-chloro-3-methylbut-2-ene) (4a) to form the basic C2o skeleton of dehydrophytol. The chloroacetate is known and prepared by the chlorhydrination of isoprene in glacial acetic acid as described in an article by W. Oroshnik and R. A. Mallory, J. Amer. Chem. Soc. 72, 4608 (1950). The coupling reaction results in the preparation of 3,7,11,15-tetramethyl-l-acetoxyhexadec-2-en-5-yne (5), a C2o enyne. The coupling reaction may be carried out employing several methods. The following methods are preferred. 

Rearrangements of propargyl esters with silver salts were first mentioned by Zakharova in the mid-1940s.49 He described the conversion of 3-chloro-3-methyl-but-l-yne into a mixture of acetates in which the allenic acetate, l-acetoxy-3-methylbut-1,2-diene, was the major compound (Scheme 3.30). Although this product could arise from a silver assisted SN2 reaction, it could also be produced from the substitution product through rearrangement, probably catalyzed by silver ions. 

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