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

Abstract

An improved method for the tert‐butanesulfinylation of diacetone glucose with tert‐butanesulfinyl chloride is reported. The method is based on a beneficial effect of catalytic DMAP, which enhances both the rate of the reaction and the enantioselectivity of the process to give (RS)‐diastereomer 2RS with a 94 % de and in quantitative yield. (RS)‐DAG sulfinate ester 2RS is an excellent intermediate for the synthesis of enantiopure tert‐butyl sulfoxides. Grignard agents and organolithium reagents can displace smoothly the diacetone glucose moiety to give synthetically relevant enantiopure sulfoxides, including highly functionalized derivatives, in high yields and with high enantioselectivities. (RS)‐DAG sulfinate ester 2RS is also an excellent N‐sulfinylating agent; simple addition of LiHMDS (lithium hexamethyldisilazide) in THF gives (SS)‐tert‐butanesulfinamide, and N‐tert‐butanesulfinylimines are then formed in a two‐step one‐pot manner. N‐Alkylated tert‐butanesulfinamides are formed by the condensation of 2RS with lithium amides.

Development of a Large-Scale Asymmetric Process for tert-Butanesulfinamide

“…Our first task was to develop a scalable process for the synthesis of 9 in good yield with high stereoselectivity and to identify a reaction medium for 9 that could facilitate the following tert -butylmagnesium chloride ( t -BuMgCl) reaction for the synthesis of 10 without isolation of 9 . The established procedure was first investigated on scale, in which 8 was treated with 1.3 equiv of thionyl chloride (SOCl 2 ) and 2.7 equiv of pyridine at −25 °C in THF, and the reaction afforded 9 with 98:2 dr in >95% yield. Upon reaction completion, the reaction mixture was diluted with EtOAc, and sodium bicarbonate (NaHCO 3 ) aqueous solution was added to quench the reaction.…”

“…Our ultimate goal is to develop a process for the production of TBSA by a more practical and economical means by overcoming the above-mentioned obstacles. The key elements to consider are avoiding low-temperature reaction conditions and replacing NH 2 Li/NH 3 with a milder nucleophile, such as lithium bis­(trimethylsilyl)­amide (LHMDS), which is an equivalent of “NH 2 ” functionality . To achieve this, we needed a new template with a sulfinate containing an active S–O bond, which can be cleaved by LHMDS.…”

Sulfinate Allenyl Carbenoids: Synthesis of 2,5‐Dihydrofurans by Domino Rearrangement and Cyclization

“…Our goal was to use propargylic sulfinates in the same way. Sulfinate esters are known to be labile, undergoing facile nucleophilic attack with species like Grignard reagents as in the Andersen synthesis of sulfoxides, and to react with amides to make sulfinamides . This makes their stability in the presence of bases and acetylides questionable.…”

Tricyclic Sulfoxide–Alkene Hybrid Ligands for Chiral Rh(I) Complexes: The “Matched” Diastereomer Catalyzes Asymmetric C–C Bond Formations

“…Arylboronic acids, LDA (purchased from Sigma-Aldrich), and DME (from TCI) were used as received. 5 , ( R S )- and ( S S )-1,2:5,6-di- O -isopropylidene-α- d -glucofuranosyl tert -butylsulfinate (( R )- 11 and ( S )- 11 ), PhLi, [RhCl­(coe) 2 ] 2 , and tert -butanesulfinyl chloride were prepared according to published procedures. LiAlH 4 (Sigma-Aldrich) was extracted in Et 2 O and used as a snow-white crystalline powder.…”