Asymmetric Addition of Terminal Acetylenes to Aldehydes, Catalyzed by Zn(OTf)₂-Cinchona Alkaloid Complexes

Abstract

Cinchona alkaloids in combination with zinc triflate ­catalyze the addition of acetylenes to aldehydes at room temperature with ee up to 89% for aliphatic aldehydes. Cinchonidine has proven to be the ligand of choice for the addition reaction whose outcome is demonstrated to be very sensitive to the alkaloid structure. Aromatic aldehydes are less reactive and give adducts of low optical purity. The more sterically hindered 2-bromo- and 2-nitro­benzaldehydes are considerably more reactive in the reaction as compared to their 4-substituted congeners.

Key words

addition reactions - aldehydes - alkaloids - alkynes - asymmetric catalysis

References and Notes

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21

In a typical experiment the reactions were run under conditions employed by Carreira and coworkers for catalytic addition of acetylenes to aldehydes in toluene. [16] Zn(OTf)₂ (0.036 g, 0.10 mmol, 20 mol%) was heated in a standard Radley reaction carousel test tube at 125 °C in vacuo (<1 mbar) for 5 h. After cooling the tube to r.t. and releasing vacuum the cinchona alkaloid was added (0.11 mmol, 22 mol%) and the mixture was evacuated for 0.5 h. To it was added dry toluene (0.5 mL) and Et₃N (0.025 g, 0.25 mmol), and the tube content was stirred for 2 h at r.t. Subsequent addition of acetylene (0.60 mmol) and stirring for 0.25 h at r.t. was followed by addition of aldehyde (0.50 mmol). The reaction was performed at r.t. or 60 °C (temperature and time are presented in Table [1] and Table [2] ). After the required reaction time, the reaction mixture was filtered through a plug of silica, using EtOAc as eluent, and the filtrate was evaporated in vacuo to give the product. The ee of the products was determined by chiral-phase HPLC analysis.