Stereoselectivity hydrogenation

As described hitherto, diastereoselectivity is controlled by the stereogenic center present in the starting material (intramolecular chiral induction). If these chiral substrates are hydrogenated with a chiral catalyst, which exerts chiral induction intermolecularly, then the hydrogenation stereoselectivity will be controlled both by the substrate (substrate-controlled) and by the chiral catalyst (catalyst-controlled). On occasion, this will amplify the stereoselectivity, or suppress the selectivity, and is termed double stereo-differentiation or double asymmetric induction [68]. If the directions of substrate-control and catalyst-control are the same this is a matched pair, but if the directions of the two types of control are opposite then it is a mismatched pair. 

After the condensation, the double bond of enamine 53 is hydrogenated stereoselectively yielding enantiopure quinolizidine 16 with trans configuration of the substituents at C-15 and C-20 as the only product. 

In order to get some informations on the effect of the support on hydrogenation stereoselectivity we carried out the hydrogenation of 4-androsten-3,17-dione 1 in toluene at 60°C and 1 atm of H2 results are collected in Table 2 and compared with those already reported for CU/AI2O3 [10). 

After careful model experiments, the lithium compound derived from 46 was coupled with the hydrazone (56) of 50 and the resulting adduct (57) was treated with the epoxide (55) to give 58, which was converted to the right half (59) corresponding to 32 mainly via hydrogenation (stereoselectivity 13 1) with Wilkinson s catalyst and ozonolysis. 

Brands and DiMichele reported the intramolecular Michael cychzation of a 1,3-dicarbonyl system (190) to alkynyl ester. The resulting double bond was hydrogenated stereoselectively to give an AC ring system (189) [97] (Scheme 16). Subsequent intramolecular aldol-type cyclization of 188 furnished a suitably substituted ABC tricychc intermediate (187). Using the same strategy, Fiirstner and coworkers synthesized an ACD tricychc intermediate (191) [98]. 

The second stereochemical aspect of alkene hydrogenation concerns its stereoselectivity. A stereoselective reaction is one in which a single starting material can give two or more stereoisomeric products but yields one of them in greater amounts than the other (or even to the exclusion of the other). Recall from Section 5.11 that the acid-catalyzed dehydration of alcohols is stereoselective in that it favors the formation of the more stable stereochemistry of the alkene double bond. In catalytic hydrogenation, stereoselectivity... 

The sense of enantioselection in other reactions can be also analyzed using the conclusions made above. Thus, the structurally rigid Rh complex of (R, R)-QuinoxP ligand (147) always has the bulky tert-hutyl substituent in the upper left quadrant, and the sense of enantioselection of asymmetric hydrogenation (stereoselection in octahedral Rh(III) complexes) is consistent with that of asymmetric addition of arylboronic acids to enones (stereoselection in square planar Rh(I) complexes) (Scheme 1.35). ... 

In this reserpine synthetic route (Scheme 3.21), Diels-Alder reaction of dihydropyridine 133 (100) and methyl a-acetoxyacrylate 134 afforded iso-quinuclidenes 135 and 136 (36). Addition of lithium r-butyl acetate to 135 afforded the )8-ketoester 137 which was converted to the corresponding enol ester 138. When 138 was refluxed in xylenes, the cis-fused hexahydroiso-quinoline 139, in which the reserpine C(15), C(16), and C(20) stereocenters are in place, formed in good yield. Hydrogenation of the enamine function in 139 followed by reduction of the enol ester afforded 140 which has the C(17)-methoxy group with the required relative stereochemistry. Acylation of ketone 140 yielded the C(18), C(19) enol ester which was hydrogenated stereoselectively to produce 141 in which the C(18) stereochemistry is set. Deprotection of the nitrogen function followed by tryptophylation afforded 142 which was then cyclized to provide the anticipated isoreserpine diol 143... 

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