Complete diastereodivergence in asymmetric 1,6-addition reactions enabled by minimal modification of a chiral catalyst

Abstract

Catalytic systems that allow selective generation of any diastereomer of a reaction product bearing multiple stereocentres through minimal modification of a single catalyst scaffold remain elusive, particularly for carbon–carbon bond formations requiring simultaneous control of multiple selectivity factors. Here, we report a catalyst-directed pinpoint inversion of diastereochemical preference in the 1,6-addition of azlactones to δ-aryl dienyl carbonyl compounds with full control over other selectivities preserved. This rigorous diastereodivergence is enabled by the slight structural adjustment of a chiral iminophosphorane catalyst, providing access to all the stereoisomers with high regio-, distereo- and enantioselectivity. The utility of this method is demonstrated in the facile stereodivergent preparation of densely functionalized proline derivatives. The experimental and computational elucidation of the origin of the diastereodivergence is also reported.

Catalyst‐Enabled Site‐Divergent Stereoselective Michael Reactions: Overriding Intrinsic Reactivity of Enynyl Carbonyl Acceptors

“…Having identified the catalyst capable of promoting a 1,4‐selective reaction with rigorous control of stereoselectivity, we turned our attention to search for a catalyst effective for overturning the regiochemical preference to 1,6‐selectivity while conserving a comparable level of stereocontrol, thereby establishing a site‐divergent stereoselective Michael reaction protocol. Toward this end, we used the P ‐spiro chiral triaminoiminophosphorane 2 as a catalyst, considering the unique ability of its conjugate acid 2 ⋅H to recognize both a nucleophile and an electrophile through hydrogen‐bonding interactions, thus providing an unusual mutual orientation in the transition state for the subsequent bond formation ,. Interestingly, the reaction of 3 a with 4 in the presence of the l ‐valine‐derived 2 a in Et 2 O at 0 °C selectively afforded 1,6‐γ‐ Z , E ‐ 5 a ( vi ) in high yield with excellent enantioselectivity (Table , entry 8).…”

Chiral phosphoric acid-catalyzed stereodivergent synthesis of trisubstituted allenes and computational mechanistic studies

“…To address this intrinsic problem, a series of ingenious strategies have been developed for asymmetric diastereodivergent catalysis [33][34][35] , such as using distinct catalysts [36][37][38] , change of metal cations 39 , and ligands 40,41 of the catalysts, change of reaction conditions 42,43 , stereodivergent dual catalysis [44][45][46][47][48][49][50] and stepwise control [51][52][53][54] . Nevertheless, achieving asymmetric diastereodivergent catalysis through modifications of one single type of chiral catalysts remains elusive 55,56 .…”

Recent Progress of Chiral Iminophosphorane Catalysis

“…并通过催化剂骨架拉近两个反应物 的距离, 从而提高反应转化率和选择性 [13] . 近年来 此后, Ooi 小组 [16,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][34][35][36][37][38][39][40][41][42][43][44][45][46] 通过类似的策略, 基于手 性氨基酸、手性联萘二胺和手性二苯乙二胺等成熟的二 胺合成子开发了一系列的手性螺环鏻盐(2～5, 图 3), 并 将其作为膦腈碱催化剂的前体用于各种各样的不对称 化学反应中, 取得了丰硕的成果. 3a, R 1 = R 2 = R 3 = Me, Ar = 4-ClC 6 H 4 X = Cl; 3b, R 1 = R 2 = R 3 = Me, Ar = Ph; 3c, R 1 = Me, R 2 = Et, R 3 = Me, Ar = Ph; 3d, R 1 = R 2 = R 3 = Me, Ar = Ph, X = t BuCO 2 ; 3e, R 1 = H, R 2 = i Pr, R 3 = Me, Ar = 4-FC 6 H 4 ; 3f, R 1 = H, R 2 = Pr, R 3 = Me, Ar = 3-MeC 6 H 4 ; 3g, R 1 = Me, R 2 = Et, R 3 = Me, Ar = Ph; 3h, R 1 = Me, R 2 = Et, R 3 = Et Ar = Ph; 3i, R 1 = Me, R 2 = Et, R 3 = Me, Ar = 3,5-Cl 2 C 6 H 3 ; 3j, R 1 = Me, R 2 = Et, R 3 = Me, Ar = 3-FC 6 H 4 ; 3k, R 1 = R 2 = -(CH 2 ) 5 -, R 3 [20][21] .…”