THE ASYMMETRICAZA-MICHAEL REACTION. A REVIEW

N‐Sulfinyl Amines as a Nitrogen Source in the Asymmetric Intramolecular Aza‐Michael Reaction: Total Synthesis of (−)‐Pinidinol

“…Metathesis reactions involving a sulfinyl group are very scarce in the literature and most of them are related to ringclosing metathesis (RCM) processes. [10] After several attempts, we were delighted to find out that the reaction of amines 3 with methyl vinyl ketone in the presence of second-generation Grubbs catalyst I and TiA C H T U N G T R E N N U N G (OiPr) 4 led to the formation of the desired CM compounds 4 in good to excellent yields in 2 h (Table 1).…”

“…General procedure for the cross-metathesis reaction: synthesis of sulfinyl amines 4, 9, 16, and 21: Methyl vinyl ketone or tert-butyl acrylate (5.0 equiv) and second-generation Grubbs catalyst I or second-generation Hoveyda-Grubbs catalyst II (10 mol %) were successively added to a stirred solution of the corresponding sulfinyl amine (1.0 equiv) and Ti-A C H T U N G T R E N N U N G (OiPr) 4 (10 mol %) in dichloromethane (0.1 m). The mixture was heated under reflux for 2 (for compounds 4, 9, and 21) or 12 h (for compounds 16) and then concentrated to dryness and purified by means of flash chromatography on silica gel by using mixtures of dichloromethane/ethyl acetate as the eluents.…”

“…17 (s, 9 H), 1.44 (s, 9 H), 1.65-1.74 (m, 2 H), 2.18-2.25 (m, 2 H), 3.03-3.22 (m, 3 H Tables 2, 3, and 6 and Schemes 4 and 10). The reaction mixture was then quenched with saturated aqueous NH 4 Cl and extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous Na 2 SO 4 , and the solvents were removed under reduced pressure.…”

“…The appropriate Grignard reagent (2.0 equiv) was slowly added at this temperature. After 1.5 h, the reaction was quenched with saturated NH 4 Cl and extracted with dichloromethane. The combined organic extracts were washed with brine, dried over anhydrous Na 2 SO 4 , concentrated under vacuum, and purified by means of flash chromatography on silica gel by using n-hexane/ethyl acetate as the eluents.…”

“…The impressive achievements made to date in the asymmetric version of this transformation rely on the use of chiral auxiliaries as the main stereochemical controllers, [4] whereas the catalytic enantioselective aza-Michael reaction remained undeveloped until very recently.…”