Introduction of angular methyl groups

The transformation of 14 into 7-methoxy-fra 5-3a,9b-dimethyl-l,3,3a,4,5,9b-hexahydro-2/f-benz[e]inden-2-one (15) illustrates the use of the sequence consisting of cyclopropanation, followed by dissolving metal reduction, for the introduction of angular methyl groups into structures containing condensed alicyclic rings. 

A soln. of crude 2-(a-bromobenzyl)-2-norbornanol in anhydrous benzene treated at 0° with 1 equivalent isopropylmagnesium bromide, and refluxed 0.5 hr. 3-phenylbicyclo[3.2.1]octan-2-one. Y 64%. A. J. Sisti, Tetrah. Let. 1967, 5327 stereospecific introduction of angular methyl groups via this reaction s. Tetrah. Let. 1969, 2269. 

Addition C C CHCR Introduction of angular methyl groups... 

The key reaction in these syntheses was the stereoselective introduction of angular cyano groups as latent methyl groups into perhydropolycyclic a, (3-unsaturated compounds. The new hydrocyanation method developed gave excellent chemoselectivity and stereochemical control. 

An example is the preparation of 18-trideuterio 5a-steroids bearing a side chain at C-17. Labeling of this position with three deuteriums was accomplished by utilizing the Johnson procedure for steroid total synthesis. This synthesis involves, in part, introduction of the 18-angular methyl group by methylation of the D-homo-17a-keto-17-furfurylidene intermediate (243). By substituting d3-methyl iodide in this step, the C/D cis- and ra/J5-18,18,18-d3 labeled ketones [(244) and (245)] are obtained. Conversion of the C/D tra 5-methylation product (245) into 18,18,18-d3-d /-3)8-hydroxy-5a-androstan-17-one (246) provides an intermediate which can be converted into a wide variety of C-18 labeled compounds of high (98%) isotopic... 

Ethers have been prepared by the thermal lead tetraaeetate method in 60-71% ° yield. Introduction of an axial 3a-acetoxy function into 5a-H steroids, however, seems to change the conformation of ring A in such a way that the distance of the 2/ -oxygen from the angular methyl group is considerably increased. Consequently the 2/5,19-ether is formed in only 0.7% to 24% yield. " 02... 

Introduction of functionalized angular methyl groups.2 The reaction of ethyl vinyl ether with 10-methyl-A1 <9 -2-octalol (1) catalyzed by mercuric acetate in a sealed Carius tube for 12 hr. at 200° gives 9-formylmethyl-10-methyl-A1-octalin (2, 85% yield) together with some dienes (3,15 % yield). Use of phosphoric acid leads only to the dienes (3). The one-step procedure involves formation of the vinyl ether followed by Claisen... 

Introduction of the cyclopropane moiety with the correct stereochemistry in the cyclopen tenone subunit was successful in creating an angular methyl group at the C/D junction of the trans-hydrindane ring system of paspalicine, an indole diterpene mould metabolite. ... 

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