Wenkert enamine

Eburnane Alkaloids. A short and highly efficient synthesis of a key intermediate Wenkert Enamine (223) for the synthesis of Eburnane alkaloids such as vincamine has been reported (126,127). 

Let us study first the epimers 1. The trans isomer (4) was prepared by reacting the so called Wenkert enamine (3) with formaldehyde. This reaction is completely stereoselective. The cis compound (5) was prepared as follows. The OH was protected by acetylation. Oxidation followed by reduction and base catalyzed hydrolysis gave rise to the desired cis compound. Of course reduction of the C=N double bond is not completely stereoselective, but the ester of the trans epimer hydrolizes much faster then the cis epimer in alkaline medium, thus the separation of the two isomers became facile. 

See Wenkert Mueller Reardon Sathe Scharf Tosi J. Am. Chem. Soc. 1970, 92, 7428 for the enol ether procedure Kuehne King J. Org. Chem. 1973, 38, 304 for the enamine procedure Conia Pure Appl. Chem. 1975, 43, 317-326 for the silyl ether procedure. 

Stork and Guthikonda (15) have shown that the cyclization of iminium ion 46 (produced in situ) gave ( )-B-yohimbine (47) and Wenkert and co-workers (22) have further observed that the acid-catalyzed cyclization of enamines of type 48 yielded exclusively product 50 via the cyclization of iminium ion 49. In the last two examples, formation of the C —C bond is the result of a trans-addition on the iminium double-bond in agreement with the principle of stereoelectronic control. 

Cyclization of an indolylethyl-tetrahydropyridine derivative is also a key stage in an extremely brief and elegant synthesis of the yohimbine ring system and a number of ajmalicinoid bases by Wenkert and his collaborators.78 Thus, internal nucleophilic attack by enolate anion at the y-position to the nitrogen atom in (122) gave a tetrahydropyridine derivative which readily cyclized to the pentacyclic enamine (123), reduction of which gave (db)-pseudoyohimbone (124) (Scheme 11). 

Aza-annulation of 104 with a variety of acrylate reagents has been utilized in the synthesis of indoloquinoiizidine alkaloid skeletons (eq. 25). Aza-annulation of 104 was affected with acrylic acid (91%), acrylic acid/DPPA (95%), acryloyl chloride/DMAP (64, 63%), and methyl acrylate (37, 52%) to generate the pentacyclic eburnane skeleton 105.42 Carbonyl reduction gave Wenkert s enamine (106), which was carried on in the synthesis of ( )-apovincamine (107) and the clinically active synthetic analog ( )-Cavinton (108).42... 

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