SmI2-promoted imino-Reformatsky reaction for facile synthesis of enantioenriched β-amino acid esters

Abstract

A facile and efficient method for the stereoselective synthesis of -amino acid esters via SmI 2 -promoted imino-Reformatsky reaction is described. Asymmetric addition of tert-butyl bromoacetate to N-tert-butanesulfinyl aldimines afforded -amino acid esters in moderate to high yields with excellent diastereoselectivities. The synthetic utilities of the tert-butyl -amino acid esters were expanded by the preparation of -lactams and 3-aminoindan-1-ones derivatives.-amino acid ester, samarium diiodide, N-tert-butanesulfinyl imine, Reformatsky reaction, -lactam, 3-aminoindan-1-one, asymmetric synthesis

Identification of Cyanamide-Based Janus Kinase 3 (JAK3) Covalent Inhibitors

“…The imine 85 was then reacted with tertbutyl bromoacetate/SmI 2 to give 86. 57,58 Treatment of 86 under acidic conditions provided the amino acid 87, which was The synthesis of sulfonamides 28−33 is described in Scheme 10. The synthesis of these analogs starts from the chiral ketone 93 which was converted to hydroxylamine derivative 106.…”

“…The organic extracts were collected and washed with brine solution, dried (Na 2 SO 4 ) and solvent was removed to provide crude 56 as a brownish liquid (4.0 g, 75% crude yield). 1 Step 2: tert-Butyl (6-Bromo-2,3-dihydro-1H-inden-1-yl)(methyl)carbamate (57). To a solution of 56 (4 g, 17.7 mmol) in DCM (500 mL) at 0 °C were added (Boc) 2 O (7.72 g, 35.39 mmol), TEA (3.58g, 35.39 mmol), and DMAP (50 mg).…”

“…Thus, 3-bromobenzaldehyde ( 84 ) was condensed with ( R )-2-methylpropane-2-sulfinamide to provide imine 85 . The imine 85 was then reacted with tert -butyl bromoacetate/SmI 2 to give 86 . , Treatment of 86 under acidic conditions provided the amino acid 87 , which was protected as the trifluoroacetamide derivative 88 . The carboxylic acid 88 was converted to the acid chloride 89 , which was subjected to Friedel–Crafts acylation to give 90 and 91 (∼3:1 ratio of regioiosmers).…”

Recent advances in the diastereoselective Reformatsky-type reaction

“…One year later, M.-H. Xu et al reported also an asymmetric imino-Reformatsky reaction using SmI 2 . 22 They optimized the reaction conditions between different arylsubstituted N-tertbutylsulfinyl aldimines 21 and the tert-butyl bromo ester 22.…”