Aldehyde Single center, enantioselective

The synthetic problem is now reduced to the development of a feasible, large-scale preparation of enantiomerically pure (/ )-citro-nellal (36), which has a single stereogenic center. One way in which the aldehyde function in 36 could be introduced is through the hydrolysis of a terminal enamine. (/ )-CitronelIal (36) can thus be traced to citronellal ( )-diethylenamine (44), the projected product of an enantioselective isomerization of prochiral diethylgera-... 

These reactions can also be made enantioselective (in which case only one of the four isomers predominates) by using539 chiral enol derivatives,540 chiral aldehydes or ketones,541 or both.542 Since both new chiral centers are formed enantioselectively, this kind of process is called double asymmetric synthesis.543 A single one of the four stereoisomers has also been produced where both the enolate derivative and substrate were achiral, by carrying out the reaction in the presence of an optically active boron compound544 or a diamine coordinated with a tin compound.545... 

The structures of the vast majority of PD-5 inhibitor compounds aimed at erectile dysfunction consist of modified purines. The structure of the recently approved drug for this indication tadalafll (113) differs markedly from the prototypes. Tryptophan methyl ester (108) provides the starting material for large scale enantioselective synthesis. Condensation of that compound with piperonal (109) in the presence of acid leads to formation of the tricyclic intermediate (110). This transform involves initial addition of the amine to the aldehyde. The carhocation from the newly formed carhinolamine then attacks the indole 2-position to form the the fused piperidine. The stereochemistry of the new chiral center is guided by that from the tryptophan carhon across the ring. The secondary amine is next acylated with chloroacetyl chloride in the presence of triethylamine to afford 111. Reaction of this intermediate with methylamine goes on to form the desired product in a single step. This reaction can he rationalized... 

Carbonyl Allylation and Propargylation. Boron complex (8), derived from the bis(tosylamide) compound (3), transmeta-lates allylstannanes to form allylboranes (eq 12). The allylboranes can be combined without isolation with aldehydes at —78°C to afford homoallylic alcohols with high enantioselectivity (eq 13). On the basis of a single reported example, reagent control might be expected to overcome substrate control in additions to aldehydes containing an adjacent asymmetric center. The sulfonamide can be recovered by precipitation with diethyl ether during aqueous workup. Ease of preparation and recovery of the chiral controller makes this method one of the more useful available for allylation reactions. 

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