Stereoselective Synthesis of 4-Amino-2,3-unsaturated-N-Cbz-imino-O-glycosides via New Diastereoisomeric N-Cbz-Imino Glycal-Derived Allyl N-Nosyl Aziridines

Abstract

The glycosylation of alcohols by the new diastereoisomeric d,l-6-deoxy-N-Cbz-imino glycal-derived allyl N-nosyl aziridines 5 and 6 affords, after deprotection of the 4-(N-nosylamino) group, the corresponding 2,3-unsaturated-N-Cbz-imino-O-glycosides bearing a free amino group on C(4) through a completely 1,4-regio- and substrate-dependent stereoselective glycosylation process.

Computational elucidation on regio- and stereoselectivity on glycosylation of alcohols by N-Cbz-imino glycal-derived allyl N-nosyl aziridines

“…The six-member ring arrangement stabilizes the transition state, decreases the mobility of the reaction sites, and allows for a more effective approximation of the nucleophile to the electrophile center. This result differs from the interaction of the -OH group with the nitrogen atom of the aziridine group proposed by Di Bussolo et al 1 (Scheme 2). However, the difference between the values of DG -( Table 1) of reactions of 1 and 3 for the formation of the anti-and the syn-isomers can be explained by distinct factors.…”

“…This difference suggests that C1 is much more reactive than C3 upon nucleophilic addition. This explains the complete regioselectivity of the reactions of 1 and 3 and agrees with the results reported by Di Bussolo et al 1 To investigate the kinetic and thermodynamic behavior of the reactions of 1 and 3, the Gibbs free energy of activation (DG -) and of reaction (DG) were calculated; the values are provided in Table 2 (see Supplementary data for additional details). The evaluation of these values shows that in the reaction of 1, the formation of the syn-isomer is kinetically and thermodynamically favored, except in 2a, which explains the formation of only one stereoisomer in each case.…”

“…Third, the different stability of the proposed transition states. The approximation of the nucleophile occurs with the help of the carbamate group by hydrogen bonding and not by the nitrogen atom of aziridine, as proposed by Di Bussolo et al 1 Lastly, the calculated values of the Gibbs free energy of activation (DG -) and of reaction (DG) show that the Hydrogen bond between alcohol and carbonylic oxygen atom (green dotted lines). Interaction between methyl group and aziridinic nitrogen atom (yellow dotted lines).…”

Nosyl (2-Nitrobenzenesulfonyl) Annulation Strategy toward Winding Vine-Shaped Bithiophenes

“…0.2 M (Scheme ; entry 1 of Table ). , The reaction was found to occur within shorter time periods to afford 8a in excellent yields (3 h, 84%; 0.5 h, 91%: entries 2 and 3). It was also found that the reaction was completed smoothly under diluted conditions (0.02 M, 97%: entry 4).…”

“…It has also been shown that the intramolecular alkylation of the nitrogen atom affords the cyclized product with a medium- to large-membered ring size despite the use of relatively concentrated conditions compared to the existing macrocyclization representative reactions, such as Yamaguchi’s lactonization . The cyclization reaction has indeed been applied to the total synthesis of several natural products bearing a medium-sized ring structure. , We envisaged that nosyl cyclization would be effective for the formation of winding vine-shaped molecules forming a 10-membered or higher ring size. If successful, this reaction can be an alternative protocol for achieving the generation of a new class of vine-shaped molecules.…”