Organocatalyzed Highly Diastereo‐ and Enantioselective Tandem Sulfa‐Michael–Mannich Reaction of 2‐Mercaptoquinoline‐3‐carbaldimines with Maleimides

Abstract

A highly diastereo‐ and enantioselective organocatalyzed domino sulfa‐Michael–Mannich reaction of 2‐mercaptoquinoline‐3‐carbaldimines with maleimides has been developed. This approach provides a convenient and efficient access to multifuntionalized tetracyclic quinoline derivatives with three contiguous stereocenters in high yield with excellent stereoselectivity (up to >99:1 dr and >99 % ee).

Organocatalytic Carbon–Sulfur Bond-Forming Reactions

“…One of the limitations of this methodology is the need to use N-arylmaleimides, because N-alkylmaleimides resulted in a decreased diastereoselectivity. An organocatalytic domino sulfa-Michael/Mannich reaction of 2-mercaptoquinoline-3-carbaldimines with maleimides catalyzed by ent-VIII gave rise to the corresponding multifunctionalized tetracyclic quinolines in 85−95% yield, 90− 99% ee, and >99:1 dr. 67 In 2012, C.-J. Wang's group used the low loading of the cinchona-derived thiourea XXXI for an efficient domino sulfa-Michael/aldol reaction of 2-mercaptobenzaldehyde 50 with α,β-unsaturated N-acyl imides 98 bearing a β-aryl and alkyl substituent to give a direct access to bioactive thiochromanes 99 in 65−94% yield, 93:7−99:1 dr, and 91−99% ee (Scheme 40).…”

Stereocontrolled Construction of the 3,4‐Dihydrothiacarbazol‐2(9H)‐one Skeleton by Using Bifunctional Squaramide‐Catalyzed Cascade Reactions

“…To explore this new tandem catalysis strategy, we examined the reaction between 9‐methylindoline‐2‐thione ( 1a )19 and N ‐cinnamoylphthalimide ( 2a )20 in dichloromethane at 20 °C as our model and evaluated the activity of a series of double hydrogen‐bond donor catalysts (i.e., I – VIII ; see Figure 1 and Table 1). All of the catalysts, including a bifunctional thiophosphonodiamide,18b,21 thioureas,22 and squaramides,23 promoted the model reaction efficiently to give the desired Michael addition/thiolysis product in acceptable yields. With regard to the enantioselectivity, the use of thiophosphonodiamide I generated the desired product 3aa with 15 % ee (see Table 1, Entry 1).…”

Thiourea–Tertiary Amine Promoted Cascade Catalysis: A Tool for Complexity Generation

“…A tandem sulfa‐Michael–Mannich reaction between 2‐mercaptoquinoline‐3‐carbaldimines 93 and maleimides 4 was reported by Zhou and his co‐workers (Scheme 25), to achieve the tetracyclic quinoline derivatives 94 by employing the thiourea catalyst C‐4 . [ 48 ]…”

“…A tandem sulfa-Michael-Mannich reaction between 2-mercaptoquinoline-3-carbaldimines 93 and maleimides 4 was reported by Zhou and his co-workers (Scheme 25), to achieve the tetracyclic quinoline derivatives 94 by employing the thiourea catalyst C-4. [48] Later in 2016, the same research group i.e., Wang group, came up with a Michael addition-transesterification double cascade between alkyl-substituted azalactones 95 and o-hydroxychalcone derivatives 96 using the bifunctional organocatalyst C-1 (Scheme 26). [49] Mechanistically, the o-hydroxychalcones 96 were activated and orientated through hydrogen bonding between the carbonyl group and the thiourea.…”