Stereospecific reactions hydrogenolysis

Reaction between the anion of 266 and propionaldehyde gave 267 as the single product. Reduction of267 by sodium borohydride to 268 was stereospecific, and hydrogenolysis of 268 provided (-l-)-/3-conhydrine (269)... 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

Treatment of the alcohol ( ) with trifluoromethylsulfonic anhydride (triflic anhydride) at -78 C afforded the ester (1 ) which could be isolated and characterized. We knew from previous experience (2J that sulfonyl esters vicinal to an isopropylidene acetal are relatively stable. The triflate T,) reacted cleanly with potassium azide and 18-crown-6 in dichloromethane at room temperature. The crystalline product [68% overall from (1 )] was not the azide ( ) but the isomeric A -triazoline ( )- Clearly the initially formed azide (18) had undergone intramolecular 1,3-cyclo-addition to the double bond of the unsaturated ester (21- ). The stereochemistry of the triazoline (1 ), determined by proton nmr spectroscopy, showed that the reaction was stereospecific. There are several known examples of this reaction ( ), including one in the carbohydrate series ( ). When the triazoline was treated with sodium ethoxide ( ) the diazoester ( ) was rapidly formed by ring-opening and was isolated in 85% yield, Hydrogenolysis of the diazo group of (M) gave the required pyrrolidine ester ( ) (90%). 

An alternative stereospecific synthesis of emetine has been accomplished from ethyl trans-5-ethyl-2-oxopiperidine-4-acetate by conversion into the lactim ether (107), which was allowed to react with 3,4-dimethoxyphenacyl bromide to give the ketone (108 R R2 = O). Reduction of this with sodium borohydride, followed by hydrogenolysis of the resulting alcohol, gave (108 R1 = R2 = H), which has previously been converted into emetine.135 The reaction of (107) with 3-benzyloxy-4-methoxyphenacyl bromide and with 4-benzyloxy-3-methoxyphenacyl bromide afforded analogues of (108 RJR2 = O), which were converted into 9-O-desmethylpsychotrine (109 R1 = H, R2 = Me) and 10-0-desmethylpsychotrine (109 R1=Me, R2 = H) respectively.136,137... 

This methodology also enables stereospecific synthesis of the side-chain of taxol [56]. The A-benzoyl-3-phenylisoserine side chain at C-13 of the taxol molecule is essential for its antitumor activity. The stereoselectivity in this reaction depends on the geometry of the silyl ketene acetal (Eq. 77). The reaction of the (E)-ketene acetal with (i )-27 produces the anti adduct with high stereoselectivity anttsyn = 98 2, 92 % de anti). In contrast, the reaction of the (Z)-silyl ketene acetal with S)-27 produces the enantiomerically pure syn adduct (symanti = > 99 1, > 99 % de syn). Aus, our methodology provides the first practical and efficient route for the preparation of both diastereomers of an a-hydroxy /3-amino ester. The syn adduct 52 is transformed to the desired A-benzoyl-(27 ,35)-phenylisoserine methyl ester by hydrogenolysis over a palladium catalyst then the Schotten-Baumann reaction. 

Hydrogenolysis of vinyloxirane is regioselective to give homoallylic alcohol 435. Hydrogenolysis of the alkenyloxirane 436 is regio- and stereospecific and proceeds by overall inversion of configuration of the allylic C—O bond to afford the homoallylic alcohol 437 [167]. Sato applied the reaction to the synthesis of an A-ring precursor of vitamin D. The protected homoallylic alcohol 439 was obtained at room temperature from the alkenyloxirane 438 in 90% yield [168]. 

This reaction is, however, of interest and preferable to catalytic hydrogenation when the resulting alcohol is prone to hydrogenolysis. Moreover, application of H—Si permits highly stereospecific reductions of certain ketones to any stereoisomeric alcohol... 

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