Enantioselective direct aminalization with primary carboxamides catalyzed by chiral ammonium 1,1′-binaphthyl-2,2′-disulfonates

Abstract

A highly effective catalytic enantioselective direct aminal synthesis was developed. Chiral ammonium 1,1'-binaphthyl-2,2'-disulfonates, which were prepared in situ from (R)-BINSA and achiral amines, promoted the enantioselective addition of primary amides to aromatic aldimines.

Synthesis of 1,1′‐Spirobiindane‐7,7′‐Disulfonic Acid and Disulfonimide: Application for Catalytic Asymmetric Aminalization

“…Screening of various amines (entries 3–8) revealed that i Pr 2 NEt was the best additive, affording 10 aa in 84 % ee . In the previous report using BINSA, 2,6‐diarylpyridines were effective additives in terms of enantioselectivity. In contrast, bulky trialkylamines were clearly better than 2,6‐Ph 2 ‐pyridine (entry 3, 14 % ee ) in this case, indicating that the chiral environment of SPISA 1 differs somewhat from that of BINSA.…”

“…To evaluate the catalytic activity as a Brønsted acid as well as the stereoinduction efficiency of 1 and 2 , we selected catalytic asymmetric aminalization of Cbz‐protected imines with carboxamides, which were previously reported using BINSA, as a model reaction. Optimization of the reaction conditions using 8 a and 9 a is summarized in Table .…”

“…We next investigated the effect of amine additives using disulfonic acid 1 as the catalyst. Formation of the mono ammonium salt of 1 was expected to improve the enantioselectivity because the ammonium moiety can increase steric bulkiness around the catalytic site without introducing ortho ‐substituents . Screening of various amines (entries 3–8) revealed that i Pr 2 NEt was the best additive, affording 10 aa in 84 % ee .…”

Asymmetric Aminalization via Cation‐Binding Catalysis

“…Chiral Brønsted acids can catalyze aminal formation reactions in high enantioselectivity with aromatic imine substrates and nitrogen nucleophiles (i.e. sulfonamides and imides) . However, aminal stereogenic centers are difficult to access, particularly with aliphatic imine substrates due to the acidic α‐protons and rapid tautomerization under acidic conditions.…”

“…sulfonamides [4a] and imides [4b] ). [4][5][6] However, aminal stereogenicc enters are difficult to access, particularly with aliphatic imine substrates due to the acidic a-protons and rapid tautomerization under acidic conditions. Therefore, chiral and strong Brønsted acids are presumably not applicable for generating aminal stereogenic centers for aliphatic imines.…”