Molybdenum‐Catalyzed Asymmetric Allylic Alkylation of 3‐Alkyloxindoles: Reaction Development and Applications

Abstract

We report a full account of our work towards the development of Mo-catalyzed asymmetric allylic alkylation reactions with 3-alkyloxindoles as nucleophiles. The reaction is complementary to the Pd-catalyzed reaction with regard to the scope of oxindole nucleophiles. A number of 3-alkyloxindoles were alkylated successfully under mild conditions to give products with excellent yields and good-to-excellent enantioselectivities. Applications of this method to the preparation of indoline alkaloids such as (−)-physostigmine, ent-(−)-debromoflustramine B, and the indolinoquinoline rings of communesin B are reported.

Pd- and Mo-Catalyzed Asymmetric Allylic Alkylation

“…Thus, simple asymmetric allylation of the oxindole in eq 32 proceeds in high yield and ee. 60 Performing this asymmetric allylation with…”

Phosphine‐Catalyzed Enantioselective γ‐Addition of 3‐Substituted Oxindoles to 2,3‐Butadienoates and 2‐Butynoates: Use of Prochiral Nucleophiles

“…In particular, oxindoles that bear an allyl‐substituted quaternary stereogenic center at the 3‐position10 have attracted considerable attention owing to their biological significance and great synthetic value. In their pioneering studies, Trost and co‐workers developed palladium‐11a,b and molybdenum‐catalyzed11c–f asymmetric allylic alkylation (AAA) reactions of 3‐substituted oxindoles to synthesize chiral 3‐allyl‐3′‐substituted oxindoles. Kozlowski and Taylor utilized Pd‐catalyzed processes for the synthesis of allyl‐substituted oxindoles 12.…”

Toward Ideal Asymmetric Catalysis

“…First, not only the Boc protecting group has a bigger molecular weight than methyl group (101 vs. 15), and the excessive atoms will not emerge into the final natural product (−)-esermethole, but also it takes three steps to prepare N-Boc protected 3-methyloxindole 10a from 4-methoxyisatin 15a via Grignard addition/Boc protection/hydrogenation, with the sacrifice of one more equivalent of (Boc) 2 O [21]. In contrast, N-methyl 3-methyloxindole 14a could be prepared easily from the corresponding indole derivative 16a [22]. Second, an extra step to reduce the Boc group by using LiAlH 4 is needed for the synthesis of (−)-esermethole, which decreased the step economy of the whole process.…”