Facile, Mild, and Highly Enantioselective Alkynylzinc Addition to Aromatic Aldehydes by BINOL/N-Methylimidazole Dual Catalysis

Abstract

The dual Lewis acid/base catalytic system, generated from N-methylimidazole (NMI), (R)-1,1'-bi-2-naphthol [(R)-BINOL], and Ti(OiPr)4, effectively catalyzes the enantioselective alkynylation of aldehydes in the presence of Et2Zn in good yields and excellent enantioselectivities of up to 94% ee at room temperature. The mild reaction conditions make it possible to use functional alkynes in this asymmetric addition.

Lewis Acid Mediated Aminobenzannulation Reactions of δ‐Ketoalkynes: Synthesis of 1‐Aminocarbazoles and 9‐Aminopyrido[1,2‐a]indoles

“…All compounds were prepared starting from 5.0 mmol of the appropriate alkyne. [34] 3-Propargyl-2-acylindoles 5a-g are new compounds and were prepared as reported in ref. [25] starting from 2 mmol of 8a,b.…”

Highly enantioselective addition of terminal alkynes to aldehydes catalyzed by a new chiral β‐sulfonamide alcohol/Ti(OiPr)4/Et2Zn/R3N catalyst system

“…However, to our knowledge, the enantioselective trimethylsilylacetylene addition of hetroaromatic, a,b-unsaturated aldehydes has attracted less attention yet. 53 In addition, only the asymmetric addition of ethynylcyclohexene to benzaldehyde has been reported, 31,34,54 and the maximum ee value is just 90%, whereas the catalytic asymmetric addition of ethynylcyclohexene to other aromatic and aliphatic aldehydes has not been yet reported. From a practical standpoint, it is still necessary to develop efficient and practical catalysts for this asymmetric transformation.…”

Highly enantioselective addition of methyl propiolate to aldehydes catalyzed by a titanium(IV) complex of a β-hydroxy amide

“…We initiated the reaction of methyl propiolate with isovaleraldehyde in the presence of 0.25 equiv chiral ligand 4a, diethylzinc, and titanium tetraisopropoxide in toluene, the expected propargylic alcohol was obtained in 75% ee (Table 1, entry 1). Some reports have shown that the Lewis bases can enhance the reaction of alkynoates with aldehydes 4c, 9,13 and that the Lewis base played an important role in this reaction. In comparison with the Lewis bases HMPA and 1,2-dimethoxyethane (DME), tertiary amine N-methylimidozole (NMI), triethylamine (TEA) and N,N,N,N-tetramethylethane-1,2-diamine (TMEDA) are stronger bases.…”