Cycloheptanone 3-methyl

The reaction of methyl propiolate (82) with acyclic enamines produces acyclic dienamines (100), as was the case with dimethyl acetylenedicarboxylate, and the treatment of the pyrrolidine enamines of cycloheptanone, cyclooctanone, cycloundecanone, and cyclododecanone with methyl propiolate results in ring enlargement products (100,101). When the enamines of cyclohexanone are allowed to react with methyl propiolate, rather anomalous products are formed (100). The pyrrolidine enamine of cyclopentanone forms stable 1,2-cycloaddition adduct 83 with methyl propiolate (82). Adduct 83 rearranges to the simple alkylation product 84 upon standing at room temperature, and heating 83 to about 90° causes ring expansion to 85 (97,100). 

Cycloheptanone Cyanoacetic acid methyl ester Ethyl bromide Hydrogen chloride... 

The same reaction sequence may be used to convert cyclo-dodecanone to cyclotetradecanone. Preparation of the pyrrolidine enamine of cyclododecanone requires 2-3 days at reflux, and reaction of the enamine with methyl propiolate is best carried out in refluxing hexane. The enamine-propiolate reaction may also be used to convert cycloheptanone to cyclononanone. In this case the procedure must be modified to provide for partial hydrogenation of the intermediate amino ester without prior hydrolysis.8 The reduced intermediate is saponified as described in the present procedure. 

The stereospecific C-alkylation of a range of benzylic ketones, such as tetralones, 2-phenylcyclohexanones and cycloheptanones, and 2-phenyl-y-lactones, has also been described [8]. For example, Af-(4-trifiuoromethylbenzyl)cinchonidinium bromide catalyses the reaction of 1,5-dibromopentane with 7-methoxy-l-methyl-2-tetralone to yield the (R)-l-(5-bromopentyl) derivative (75% yield with 60% ee). 

Syntheses of diastereomerically pure racemates of himachalene derivatives started from cycloheptanone G (Fig. 9). The sequence to I involved dimethyla-tion to yield H followed by bromination/dehydrobromination and conjugate methylation using cuprate chemistry. The sequence furnishing L and M follows a Robinson-annelation type Reaction of I with 3-(trimethylsilyl)but-3-en-2-one yielded K. Refluxing K with potassium hydroxide in ethanol removed the silyl group and cyclized the diketone to form a 97 3 mixture of racemic L and M. Occurring as a volatile in A.flava, L served as a versatile intermediate in the syntheses of other Aphthona compounds. 

TABLE 15. Synthesis of 2-methyl-2-(substituted)cycloheptanones (199) from cyclohexanone derivative 195,1-chloroethyl /j-tolyl sulfoxide, and electrophiles... 

The procedure reported here provides a convenient method for the a-hydroxylation of ketones which form enolates under the reaction conditions. The reaction has been applied successfully to a series of para-substituted acetophenones, 1-phenyl-1-propanone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclododecanone, 2-methyl cyclohexanone, 2-norbornanone and benzalacetone. In the case of a steroidal example it was shown that a carbon-carbon double bond and a secondary hydroxyl group are not oxidized. A primary amino function, as in the case of p-aminoacetophenone, is not affected.5 Similarly, a tertiary amino ketone such as tropinone undergoes the a-hydroxy at ion reaction.5... 

Methylcyclohexanone and suberone (cycloheptanone) oximes correspondingly give 7-methyl-4,5,6,7-tetrahydroindole (33, yield 70%), its N-vinyl derivative [34, yield 80% (75MI1)], and 4,5,6,7,8-pentahydro-l//-cyclohepta[6]-pyrrole [35, yield 79% (76MIP1 80KGS1299)] (Table XIX). 

Presumably, the methyl sulfoxide was chosen here because it worked better—it is more usual to use a phenyl sulfoxide, and PhS groups can be introduced in the same way (by reacting enolates with PhSSPh or PhSCl). The cycloheptanone derivative used in our first elimination example was made from cycloheptanone in this way. 

Aryl-substituted ketones react directly with elemental sulfur in hexa-methylphosphorus triamide with formation of l,2-dithiole-3-thiones.46,47 Aryl-substituted acetaldehydes can condense likewise with carbon disulfide to give the analogous 4-aryl-substituted l,2-dithiole-3-thiones.48 The same reaction was observed with aryl-substituted acetic acid esters, in which a methylthio group is incorporated into the reaction product (26).49 Thioketones and enthioles react analogously. 50,51 The parent l,2-dithiole-3-thione (27) has been prepared from the tetra-methyl acetal of malondialdehyde and phosphorus pentasulfide.52 In the presence of ammonia the reaction of cyclohexanone or cycloheptanone with carbon disulfide and sulfur gives as by-products the condensed 1,2-dithiole-3-thiones 28a and 28b, respectively.53... 

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