Enantioselective direct Mannich-type reactions of 2-benzylpyridine N-oxides catalyzed by chiral bis(guanidino)iminophosphorane organosuperbase

Abstract

2-Benzylpyridine N-oxides possessing less acidic α-protons were utilized as pronucleophiles for the first time in enantioselective addition reactions under Brønsted base catalysis.

Phosphorus‐Containing Superbases: Recent Progress in the Chemistry of Electron‐Abundant Phosphines and Phosphazenes

“…The good availability of chiral phosphazenes [127] and their outstanding catalytic activity in enantioselective sulfa‐Michael addition reactions, [128] Mannich‐type reactions, [129] cycloaddition reactions, [130] hydrophosphinylations [131] as well as 1,2‐ and 1–4‐addition reactions [132] among others has moved them into the focus of current interest. Rigid chiral iminophosphoranes are excellent reagents for challenging enantioselective reactions as well [133] .…”

“…The chiral iminophosphoranes 40 of Dixon,[ 128 , 132 , 134 , 135 ] spiro‐phosphazenes 41 of Ooi[ 125 , 136 ] and chiral guanidinophosphazenes 44 and 45 of Terada[ 129 , 130 , 131 , 137 , 138 , 139 ] are depicted in Scheme 17 , but will not be discussed in more detail, since latest advances and achievements have been reviewed recently. [ 126 , 140 ] The chiral phosphazenes 43 and 42 of Suna [141] and Anders [142] are also included (Scheme 17 ).…”

“…The employment of chiral organocatalysts bearing strongly Brønsted basic phosphazene moieties for the activation of only weakly acidic pronucleophiles has been introduced for the first time in the asymmetric Henry reaction by Ooi et al in 2007. [125,126] The good availability of chiral phosphazenes [127] and their outstanding catalytic activity in enantioselective sulfa-Michael addition reactions, [128] Mannich-type reactions, [129] cycloaddition reactions, [130] hydrophosphinylations [131] as well as 1,2-and 1-4addition reactions [132] among others has moved them into the focus of current interest. Rigid chiral iminophosphoranes are excellent reagents for challenging enantioselective reactions as Scheme 14.…”

Activating Pronucleophiles with High pKa Values: Chiral Organo‐Superbases

“…Recently, they continued to use this kind of superbase to abstract the benzylic hydrogen atom of the 2‐benzylpyridine N ‐oxides 47 for the Mannich‐type reaction to N ‐Boc‐aldimines (Eq. 3, Scheme ), as well as deprotonating the α‐hydrogen atom of the sulfonyl group in the β,γ‐epoxysulfones 49 for the formal [3+2] cycloaddition (Eq. 4.…”

Recent Progress of Chiral Iminophosphorane Catalysis

“…此后, Terada 小组 [48] 利用螺环膦腈碱前体 6 催化了 亚胺与各种各样底物的 Mannich 反应, 立体选择性生成 相应的旋光纯的胺类化合物, 该产物可以作为手性合成 子应用于各种旋光碱的合成(Scheme 8). 膦腈碱 6a 生成 的强碱催化剂能够脱去 2-苄基吡啶 N-氧化物苄位的质 子而生成碳负离子, 从而与亚胺发生加成反应, 以中等 到优秀的立体选择性高效得到手性目标化合物(Scheme 8).…”