A General and Expeditious One-Pot Synthesis of Sulfoxides in High Optical Purity from Norephedrine-Derived Sulfamidites

Abstract

A general and simple procedure for preparing any kind of enantiomerically enriched sulfoxide starting from norephedrine-derived N-benzyloxycarbonylsulfamidite 3a is reported. After one-pot reaction of 3a with RMgX, HBF(4), and R'MgX, a variety of sulfoxides 6 are obtained in ee usually higher than 93% and isolated yields ranging between 50 and 78%. The obtained configuration is tunable by simply electing the order of the addition of the reagents. [reaction--see text]

Sulforaphane homologues: Enantiodivergent synthesis of both enantiomers, activation of the Nrf2 transcription factor and selective cytotoxic activity

“…As an alkyl methyl sulfoxide, the synthesis of enantiopure sulforaphane is not straightforward [46][47][48][49], and the main approximations for the synthesis of enantiomerically pure sulfoxides developed so far fail in the preparation of simple dialkyl sulfoxides. Actually, there is no asymmetric catalytic oxidation able to give 10 enantiomerically pure dialkyl sulfoxides from the corresponding prochiral thioethers [50].…”

Enantioselective Routes to Sulfoxides Based Upon the Use of Carbanionic Leaving Groups

“…[12] Very recently, improved protocols of this double displacement strategy have been reported. Garcia Ruano et al [13] introduced the use of an N-acylated sulfamidite prepared from norephedrine. Organometallic reagents were used to cleave first the sulfur-nitrogen bond and then the sulfuroxygen bond.…”

DMAP‐Catalysed Sulfinylation of Diacetone‐D‐Glucose: Improved Method for the Synthesis of Enantiopure tert‐Butyl Sulfoxides and tert‐Butanesulfinamides

“…However, it has been difficult to synthesize methyl tert ‐butyl sulfoxide in enantiopure form. Furthermore, the stereochemical outcomes proposed for the reactions of tert ‐BuMgBr with various sulfinylating agents were contradictory,22,27,31–33 and consequently the absolute configuration of the final methyl tert ‐butyl sulfoxide was confusing.…”

“…In this regard, the sulfite methodology, a diastereoselective approach reported by Kagan in 1991, was the first approach to solve some of the limitations of the traditional Anderson method for the synthesis of optically pure dialkyl sulfoxides, and it was particularly suitable for the synthesis of hydroxysulfinate 1 en route to tert ‐butyl sulfoxides 21. The regioselectivity problems associated with Kagan's approach were elegantly solved by the Garcia‐Ruano22 and Senanayake23 groups, who, almost at the same time, developed three‐step approaches using activated 1,2,3‐oxathiazolidine‐2‐oxides as intermediates for the synthesis of the corresponding tert ‐butanesulfinate esters (i.e., 4 and 5 ). Of the limited number of enantiopure tert ‐butanesulfinylating agents developed to date,24 the most widely used is tert ‐butyl tert ‐butanethiosulfinate ( 3 ).…”