Absolute configuration of conhydrine

Abstract

Catalytic hydrogenation of optically active 2-pyridyl ethylcarbinol (1) formed the alkaloid conliydrine (2) stereospecifically. Application of the von Braun reaction gave conversion of (+)-conliydrine into R-(-)-3-octyl benzoate and of (-)-conliydrine into tlie S-(+)-antimer. Both the relative and absolute configuration of the two asymmetric centers in natural (+)-conhydrine have been determined by the combined use of optical rotatory dispersion (0.r.d.) and circular dicliroism (c.d.). The results are in agreement with other physical and clieniical evidence.Canadian Journal of Chemistry, 47, 4393 (1969) The alkaloid conhydrine was isolated from Coniunz maculatum and natural (+)-conhydrine was oxidized to L-(-)-pipecolic acid (1). The relative configuration of the two asymmetric centres in conhydrine is regarded as erythro on the basis of chemical evidence (2, 3) identifying the octan-3,4-diol obtained from (+)-conhydrine by Hofmann degradation and hydrogenation of the methine base (4) with racemic erythro-octan-3,4-diol.Since this work was done on the racemic alkaloid, and the conclusions are based on assumptions regarding the stereochemistry of the intermediate steps, it was desirable to obtain further evidence concerning the configuration of the carbiiiol carbon. This has now been achieved both by chemical means and by the 0.r.d.-c.d. method previously applied (5) to the configuration of tlie sedridine and allosedridine alkaloids.The catalytic hydrogenation of optically active (+)-2-pyridyl ethylcarbinol(1) under conditions identical to those used (6a) for tlie reaction forming sedridine gave, by asymmetric induction, (+)-conhydrine (2) as the major product (66).

Reaction of diethyl bromomalonate with sodium phenoxide

“…The reaction of 1 with sodium phenoxide was carried out in the following solvents: absolute alcohol, 85% alcohol, tetrahydrofuran, benzene, and ether. In addition to the previously reported aroxymalonates (2a and 3a), the crude reaction product was found to contain the tetracarboxylates 4 and 5, together with diethyl malonate (6), diethyl -bromophenoxymalonate (7) , and hexaethyl 1,1,2,2,3,3-propanehexacarboxylate C6H6OC (COOEt )2 (EtOOC)2CHC(COOEt)2CH (COOEt), Br 7 8 (8) . The results of our experiments are summarized in Table I. "…”

“…The latter then combines with the bromine of a second molecule of 1 to give malonate anion (10) and dibromomalonate (11). (8) The possibility of 2a as an intermediate in the formation of 3a has been excluded on the basis of the reaction of 1 with sodium phenoxide in the presence of 4-nitrophenoxy malonate. There was no evidence for the formation of phenoxy (4-nitrophenoxy) malonate.lb…”