Regio‐ and Stereoselective Stevens Rearrangement of Benzyltetrahydroprotoberberinium Salts

Abstract

8‐(Arylmethyl)berbines are conveniently obtained through a Stevens rearrangement of the corresponding N‐arylmethylberbinium salts with sodium methylsulfinylmethylide in DMSO. This procedure has provided two new nonnatural 8‐benzylcanadines stereoselectively, without competition from the Hofmann elimination. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

From Berbines to Protopines: Regiocontrolled Hofmann Elimination/Hydroboration/Oxidation of N‐Substituted Berbinium Salts

“…As we established previously, [9] the use of mediumstrength bases with hydroxylic solvents (e.g., MeONa/ MeOH) preferentially yields the Hofmann elimination products. On the other hand, strong bases in highly polar nonprotic solvents (e.g., HNa/DMSO) favour the Stevens rearrangement, while the use of these bases in the presence of apolar solvents (e.g., HNa/benzene) leads to an increase in the yield of elimination products.…”

“…[9,10] Treatment of the (±)-N-benzylberbinium salts with base produced a complex mixture as a result of the competition between the two processes indicated in Scheme 2.…”

“…In order to perform this objective, we initially chose (±)-N-benzylcanadinium bromide [9] (1a) as the model compound (Scheme 3). To raise the yield of the Hofmann [a] Reaction conditions: substrate (0.5 mmol), base (4.5 mmol), solvent (2 mL).…”

“…Remarkably, by using dimsylsodium and DMSO the Stevens rearrangement became the dominant pathway yielding the 8-substituted berbines with no competition from alternative reactions. [9] This process occurred through regioselective hydrogen abstraction to generate exclusively a C-8 ylide which rearranged in a stereoselective manner to generate 8-(arylmethyl)berbines.…”

Sodium Methylsulfinylmethylide: A Versatile Reagent

“…12 (I) Carboxylate-stabilized sulfur ylide generated in the presence of sodium methylsulfinylmethylide reacts directly with aldehydes and ketones to give epoxides in DMSO or THF-DMSO mixtures.…”