Role of Additives in Chiral Amine-Catalyzed Direct Aldol Reaction

Abstract

A systematic study of chiral adducts derived from amines as catalysts for aldol reaction revealed that enantioselective outcome depends on the chiral enamine intermediate and not the face-selective activation of aldehyde. A simple addition compound of proline and 8-hydroxy quinoline was found to be a good catalyst.

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GRAPHICAL ABSTRACT

Keywords:

• Additives
• aldol reaction
• chiral amines
• organocatalyst
• pyrrolidine-catalyzed

ACKNOWLEDGMENTS

Financial support for this work was provided by the National Chemical Laboratory (CSIR) through the “in-house” program. One of us (R.L.S.) thanks the Council of Scientific and Industrial Research, New Delhi, for a research scholarship. We are thankful to S. Kunte for chiral HPLC analysis.

Notes

^a Isolated yield.

^b Determined by HPLC analysis.

^c Reaction was done at 25 °C.

^a Acetone as the solvent.

^b 10 mol% chiral amine achiral acid combination (1:1).

^c Isolated yield.

^d Determined by chiral HPLC analysis.

^e Reported^{[ 22 ]}using 20 mol% of catalyst.

Note. A, benzoic acid; B, PTSA; C, salicylic acid; D, (±)-BINOL.

^a Ten equivalents of donor reactant were used under neat conditions and two equivalents when a solvent was used.

^b Isolated yield.

^c Determined by chiral HPLC analysis.

^d Reported^{[ 3 ]} using 30 mol % of proline.

^e 3 vol% water in DMF.

Notes. A, 2-amino phenol; B, 8-hydroxy quinoline.

^a Ten equivalents of donor reactant.

^b Isolated yield.

^c Determined by chiral HPLC analysis.

^a Isolated yield.

^b Determined by HPLC analysis.

^c Determined by chiral HPLC analysis (major/ minor).