Simple Enantiospecific Synthesis of Sulfides of Cinchona Alkaloids

Abstract

The native and epi-Cinchona alkaloids were reacted with (ArS)₂/Bu₃P in toluene at 65 °C to give the corresponding arylsulfanyl derivatives (15 examples, 31-75%) with complete inversion of configuration at 9-C stereogenic centers. Similar products were also obtained in the enantiospecific nucleophilic substitution of the 9-mesylates of alkaloids with sodium thiolates (4 examples, 73-84%) and no cinchona rearrangement was observed. The chiral thioethers obtained were preliminarily tested as N(sp³), S-donating chiral ligands in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenylprop-2-enyl acetate and gave the product with up to 78% ee.

Key words

asymmetric synthesis - chiral pool - ligands - stereoselectivity - sulfur

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11

For experimental details, see reference 7i.

12

Resonances for the allylic and C-8 carbons coincide at this signal.