Science of Synthesis

Burns, N. Z.; Jacobsen, E. N., Science of Synthesis: Stereoselective Synthesis, (2011) 2, 831.

Ohsawa has reported the proline-catalyzed addition of ketones to dihydro-β-carboline ‌122‌ to give chiral 1-substituted tetrahydro-β-carbolines ‌123‌ in high optical purity (‌Scheme 45‌).[‌68‌] The ketone nucleophile is used as partial cosolvent (it makes up 20% of the solvent volume) and an optimal amount of 50 equivalents of water are necessary for high selectivities and to facilitate catalyst turnover. Only acetone, butan-2-one, and pentan-2-one are reported to give useful results with low catalyst loadings, and in the latter two cases a reaction time of 5 days is necessary. In the reaction with methyl vinyl ketone and 50 mol% proline, the product is obtained with an additional ring from conjugate addition of the carboline nitrogen in 76% yield and 92% ee. Such structures are found in numerous indole alkaloid natural products.

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References