Ketones, reductive cleavage regioselectivity

Sauers and coworkers have applied the Paterno-Biichi reaction to engeneral formula 427 (Scheme XXXIV) Reductive cleavage of these products with lithium aluminium hydride is also regioselective and leads, following oxidation, to ketones... 

Trifluoropropcnc itself reacts regioselectively with various nitrile oxides, even nonaromatic nitrile oxides. The latter arc prepared in one step from oximes and A -chlorosuccin-imide, or in a two-step sequence with isolation of the hydroximoyl chlorides. Cycloadducts, obtained at room temperature in the presence of triethylamine, are then converted into trilluoro- 8-hydroxy ketones 9 by reductive cleavage. The reaction with a dipole substituted by a group derived from L-phcnylalanine allows the preparation of chiral ketones. ... 

One of the most useful methods for the transformation of ketones into alkenes is conversion of the ketone, via enolate formation, into a vinyl-OR derivative and subsequent reductive cleavage of the sp oxygen bond. Because there are a number of ways to generate either the kinetic or thermodynamic enolate selectively, this route offers one of the most important ways of introducing the alkenic double bond with excellent control of regioselectivity. 

Condensation reactions with donor species generated by reductive cleavage of a-sub-stituted carbonyl compounds are regioselective. Thus, the synthesis of a-(l-hydrox-yalkyl)-P-ketols is quite straightforward from a, 5-epoxy ketones. Samarium enolates derived from a-(pyridylthio)glycyl peptides are also applicable to the synthesis of unnatural peptides by reaction with various carbonyl compounds. ... 

Unlike the corresponding phosphonium salts, addition of sulfonium salts to aldehydes results, not in the alkene products, but in the formation of epoxides (see Section 1.1.5.2). However, sulfones can be used to prepare alkenes, by way of the a-metallo derivatives, in what is termed the Julia olefination (alkenylation). Addition of the organometallic species to an aldehyde or ketone gives a p-hydroxy sulfone which, in the form of its 0-acyl or 0-sulfonyl derivative, undergoes reductive cleavage with, for example, sodium amalgam in methanol to form the alkene. The reaction is regioselective and can be used to prepare mono-, di- and trisubstituted alkenes (2.91). 

The next task was to convert 42 to ketone 44. This transformation called for a regioselective hydration of the C13-C14 olefin. This was accomplished by vicinal dihydroxylation of the olelin, which was accompanied by formation of the y-lactone (rather that the d lactone). The preference for y-lactonization (which is most often the case in such simations) left the C14 hydroxyl group free for oxidation to ketone 43. Reductive cleavage of the a-C-O bond, and esterification of the resulting acid, gave 44 (see 99 to 100 in Alkaloids-12 for comparison). 

Cleavage of cyclopropyl ketones.8 Cyclopropyl ketones are converted by lSi(CH3)3 under very mild conditions into y-iodo ketones. The regioselectivity is usually high and is similar to that observed in lithium-ammonia reductions. 

Gribble and Saulnier (79) have extended their ellipticine synthesis 43) to the synthesis of 9-methoxyellipticine (2) (Scheme 24). One of the key features of this approach is the regioselective nucleophilic addition to the C-4 carbonyl group of pyridine anhydride 28. The other noteworthy transformation is the conversion of keto lactam 142 to the diol 143 with methyllithium, a process that presumably involves cleavage of the initial adduct to a methyl ketone which undergoes cyclization at the C-3 position of the indolyl anion. Reduction of 143 with sodium borohydride completes the synthesis of 2, in 47% overall yield from 5-methoxyindole (139). Gribble and students 80) have also used this method to synthesize 8-methoxyellipticine (134), 9-fluoroellipticine (144), and the previously unknown 7,8,9,10-tetrafluorellipticine (145), each from the appropriate indole. 

Some examples of regioselective alkylations of simple ketones are presented in Scheme 1.6. These examples illustrate the most useful modes of enolate generation, including deprotonation (entries 3 and 4), enone reduction (entries 1, 2, and 5), and cleavage of silyl enol ethers (entries 6 and 7). 

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