N-Substituted tertiary and O-substituted quaternary carbon stereogenic centers by site-, diastereo- and enantioselective vinylogous Mannich reactions

Abstract

A readily accessible small-molecule phosphine, derived from commercially available starting materials such as an enantiomerically pure amino acid, serves as the precursor to a Ag-based chiral complex that can be prepared and used in situ to promote a variety of enantioselective vinylogous Mannich (EVM) reactions that involve siloxypyrroles as reaction partners. Transformations with unsubstituted nucleophilic components proceed efficiently and with exceptional site- (γ vs α-addition), diastereo- and enantioselectivity [up to 98% yield, generally >98:2 γ/α and diastereomeric ratio (dr) and up to 99:1 enantiomeric ratio (er)]. The first examples of efficient, diastereo- and enantioselective vinylogous Mannich additions with 5-methyl-substituted siloxyfuran, resulting in the formation of O-substituted quaternary carbon stereogenic centers are presented as well. Appreciable efficiency and diastereo- and enantioselectivity (up to >98:2 dr and >99:1 er) is accompanied by formation of α-addition products that can be oxidatively removed

Direct Catalytic Asymmetric Mannich‐type Reaction of α,β‐Unsaturated γ‐Butyrolactam with Ketimines

“…Quinuclidine and DBU have nucleophilic characteristics that promote the reaction, implying an MBH mechanism for enolate formation (entries 9 and 10); much less nucleophilic Et 3 N exhibited steady reaction progress to give the α‐adduct 3 a (entry 7) . Together with the exclusive formation of α‐adduct 3 a with lithium aryloxide as Brønsted base (entry 8), the dienolate formation/α‐addition/isomerization sequence was likely operative to afford MBH‐type α‐adduct 3 a . Lowering the reaction temperature led to improved enantioselectivity (91 % ee ; entry 11) .…”

“…[19] To gether with the exclusive formation of a-adduct 3a with lithium aryloxidea sB r ønsted base (entry 8), [20] the dienolate formation/a-addition/isomerization sequence was likely operative to afford MBH-type a-adduct 3a. [21] Lowering the reaction temperature led to improved enantioselectivity (91 % ee;e ntry 11). [22] Et 3 Ni sa ni nexpensive common amine base, and the use of 2equiv of Et 3 Na t ah igherc oncentrationa fforded 3a in 94 %i solated yield with 90 % ee (entry 12).…”

A Decade of Advance in the Asymmetric Vinylogous Mannich Reaction

“…Finally, the same authors reported the first example of an asymmetric VMR with 5-methyl-substituted silyloxyfuran 12, resulting in the formation of butenolides 14 bearing an O-substituted quaternary stereogenic center (Scheme 5). 13 Addition to different aldimines 13 proceeded with high diastereo-and enantioselectivity although variable amounts of α-addition products were detected, probably due to the lower nucleophilicity and accessibility of the γ site.…”

“…Additions to aryl-and alkynyl-substituted aldimines 10 took place in good yields, furnishing compounds 11 bearing two contiguous N-substituted stereogenic centers with exceptional site-(γ-vs α-addition), diastereo-and enantioselectivity (Scheme 4). 13 Scheme 4 Asymmetric Ag-catalyzed VMR of aryl-and alkynyl-substituted aldimines 10 and N-Boc TMS-silyloxypyrrole 9…”

Synthesis of Symmetric Chiral Aminophenol Compounds

“…[8]的不对称加成、Mannich 反应[9]、亚胺的烯丙基化反应[10] [11] [12]等多种反应中都表现出良 INOVA-600 型核磁共振仪(以 TMS 为内标，CDCl 3 为溶剂)；Brucker Equinox 55 FT-TR 型红外光谱仪 (KBr 压片)；Brucker 型质谱仪(ESI 电离技术)；低温实验使用 EYELA PSL-1810 型磁力搅拌低温恒温水槽 (无水乙醇为介质)。 实验所用试剂均为分析纯，石油醚沸程为 60℃~90℃，其中，无水四氢呋喃是在钠砂中惰性气体保护 下加热回流并用二苯甲酮显色；柱层析硅胶 G (青岛海洋化工有限公司)；薄层层析硅胶 GF254 (青岛海洋 化工有限公司)；薄层层析板(GF254，加 0.5% CMC 自制)，紫外灯下(254 nm)观测并用碘蒸气显色。 2.2. 氨基酚化合物的合成 以化合物 7A 的合成为例[10]： 50 mL 圆底瓶中加入化合物 1A (0.23 g, 2 mmol)，添加混合溶剂(20 mL, V 1,4-二氧六环:V 水 = 1:1)搅拌使其 溶解溶液。冰浴条件下分批加入(Boc) 2 O (1.09 g, 5 mmol, 2.5 equiv.…”