Fig. 3: Scope of asymmetric Mannich/Wittig/cycloisomerization sequence. | Nature Communications

Fig. 3: Scope of asymmetric Mannich/Wittig/cycloisomerization sequence.

From: Modular synthesis of chiral 1,2-dihydropyridines via Mannich/Wittig/cycloisomerization sequence that internally reuses waste

Fig. 3

Reaction conditions. Mannich step: imines 4 (0.5 mmol), aldehydes 5 (1.0 mmol), L-proline (20 mol%), CH3CN (10 mL), 0 °C, 20 h. Wittig step: ylides 6 (1.0 equiv based on the crude 7), EtOAc (2 mL), 80 °C, 15 h. Cycloisomerization step: SiCl4 (30 mol%), EtOAc (2 mL), 40 °C, 2–10 h. Unless otherwise noted, overall yields for 3 steps are given. Ee values were determined by chiral HPLC analysis. *These reactions begin from the corresponding isolated chiral β-amino aldehydes 7 and the yields for two steps are given. †Using 1.0 equiv of 5. ‡Using SiCl4 (45 mol%) instead of SiCl4 (30 mol%). For details, see the Supplementary Information. a Synthesis of 2,3,6-trisubstituted 1,2-dihydropyridines. b Synthesis of 2,3- and 2,6-disubstituted 1,2-dihydropyridines. c Synthesis of 2-substituted 1,2-dihydropyridines. d Typical examples with isatin-derived N-Boc ketimines.

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