Synthesis of α-thiohemiaminal derivatives of deoxynupharidine

Abstract

Disulfides, sulfenyl chlorides, thiosulfonates, and sulfensuccinimides were evaluated as electrophilic thiating agents for converting the enamine 6-dehydrodeoxynupharidine to α-thiohemiaminal derivatives of the alkaloid deoxynupharidine. Sulfensuccinimides were generally the most useful but other types of agents produced better yields in some individual cases.

Synthesis of (−)-Neothiobinupharidine

“…Notably, this proposed biosynthesis does not account for distribution of these stereoisomeric compounds in nature. For instance, monomeric enamines similar to 6 have been shown to react preferentially with electrophiles on their convex face (Figure c), − but this selectivity for the C–C (Mannich-type) and C–S (sulfenylation) bond forming reactions of 6 and 7 would lead to a stereochemical outcome which has never been observed ( 4a – d ) in Nuphar sp. , …”

“…The stereoselectivity of dimerization deserves some discussion. Nuphar quinolizidines have been shown to react stereoselectively on the convex face. − This facial selectivity is observed for the initial Mannich-type reaction between 5 and 6 , with an average 4.5:1 preference for convex versus concave Mannich ( 3d + 4d : 1d + 2d , Table ). However, the subsequent concave -face enamine sulfenylation ( 16 ) that must occur to form 3a as the major product is more difficult to rationalize since the stereoselectivity of this process is dependent on both solvent choice and equivalents of polysulfide.…”

Thiosulfonates as Emerging Reactants: Synthesis and Applications

“…Silanes were used as proton source. S ‐Phenyl benzenethiosulfonate ( 10 ) has also been used to convert the enamine functionality in 6‐dehydrodeoxynupharidine ( 216 ) to the corresponding diastereomeric mixture of α‐phenylthiohemiaminals ( 217 , 218 ), which are active against human pathogenic fungi (Scheme ) . α‐Phenylthiohemiaminal is obtained from the reaction of S ‐phenyl benzenethiosulfonate ( 10 ) with the enamine followed by quenching with KOH.…”

Catechol monoether synthesis

“…RO HO CH=CH, OTMS RO>/CH=CH, fr + 2 (2) 5 6 Aldehyde 6 was the only product when 5 was treated with tetra-n-butylammonium fluoride in tetrahydrofuran. Since the palladium-catalyzed oxygenation of 6 produced a mixture of products, it was necessary to find an efficient route to 2.…”