ortho-Metalation of Enantiopure Aromatic Sulfoxides and Stereocontrolled Addition to Imines

Abstract

Enantiopure aromatic (phenyl, naphthyl) and heteroaromatic (pyridyl, quinolyl, diazinyl) sulfoxides have been synthesized by reaction of (S)-tert-butyl tert-butanethiosulfinate with aryl- or heteroaryllithium derivatives. The ortho-directed metalation of the sulfoxides was performed with lithium bases. Subsequent addition of the lithiated intermediates to N-tosylimines afforded tosylaminoalkyl tert-butylsulfinyl arenes. In most cases a complete asymmetric induction was highlighted in favor of (S,S) isomers. Heating the aminosulfoxides provided an original cyclization to form novel cyclic sulfenamides. A novel enantiopure synthesis of a benzylamine was described. An application of an enantiopure aminosulfoxide as N,S ligand for the asymmetric catalysis of allylic nucleophilic substitution has been successfully tested.

Catalytic Generation of Cesium Acetylide by CsF: Synthesis of 1,3-Benzothiazines from Cyclic Sulfenamides

“…The scope of the reaction was next explored with a range of aryl- and alkylsulfenamides bearing different protecting groups on the nitrogen atom (EWG = Ts, SES or Boc). The required isothiazolines 1a − d , 13b and 14a,c were prepared according to our described procedure (Scheme ): ortho -metalation of enantiopure sulfoxide 9 followed by addition of imine or sulfone (Table ) . New aminosulfoxides 10 − 12 were obtained with complete diastereocontrol when R 1 is an alkyl group (entries 1, 2, 5, 6).…”

Diastereoselective Addition of Enantiopure Lithium tert-Butylsulfinylferrocene to Imines

“…Examination of possible approaches of the sulfinyl carbanion and the imine led us to consider a concerted four-membered transition state A , as first proposed by Garcia Ruano's group and then by us (Scheme ) . It cannot be applied in the ferrocene series.…”

Synthesis of 3-Substituted Aryl[4,5]isothiazoles through an All-Heteroatom Wittig-Equivalent Process

“…We recently reported a mild and general procedure for the synthesis of sulfoxides, sulfinic acid esters, and sulfonamides that uses tert -butyl sulfoxides as the sulfinyl source through activation by N -bromosuccinimide (NBS) and acetic acid at room temperature . To expand the application of this procedure, we utilized it for the synthesis of chiral 2,3-dihydrobenzisothiazole-1-oxide 4 (Scheme ) from the starting material, 3 , which is readily accessible from ortho metalation of aryl sulfoxides 1 and asymmetric addition to imines 2 . However, upon treatment of 3a (R 1 = none, R 2 = Ph in Scheme ; also see Table ) with NBS and acetic acid, the corresponding compound 4 was not isolated.…”