Introduction Methyl groups, angular

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... 

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. 

Except for aromatization, the 14a-demethylation of lanosterol 64 seems to operate by the same sequence of events in order to remove the angular C(14) methyl group with concomitant introduction of the C(14) double bond to furnish 65 (Fig. 12). 

Angular methylation. A recent synthesis 11-ketoprogesterone (6) requires introduction of the C, j-methyl group into the p,"y-unsaturated ketone 1, obtained by Birch reduction of a precursor with an aromatic ring A Reaction of 1 with CH,l,/C,H,ZnI, the Sawada modification of the Simmons-Smith rc.igcnt, is not successful, and the diethyl... 

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. ... 

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. 

Three approaches to the synthesis of 69 have been described." The first approach entailed the stereoselective introduction of the C-8a angular methyl group. The required starting material was the methoxy enone 71, prepared in 24% overall yield by a five-step sequence from 2-methyl-1,3-cyclohexanedione and l,4-dimethoxy-2-butenone, via annelation and reductive removal of the allylic oxygen." ... 

The second and ultimately most practical sequence involved the introduction of the C-4a angular methyl group via the Nagata hydrocyanation reaction on the enone (85) (Scheme 11). Robinson annelation between the enone (84) and... 

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. 

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