Catalytic enantioselective addition of terminal alkynes to aromatic aldehydes using zinc-hydroxyamide complexes

Abstract

A mandelamide ligand, derived from (S)-mandelic acid and (S)-phenylethanamine, catalyzes the addition of aryl-, alkyl- and silyl-alkynylzinc reagents to aromatic and heteroaromatic aldehydes with good yields and good to high enantioselectivities.

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“…The product can be easily desilylated to give the corresponding terminal alkynol, which can further be used as the precursor to carry out the alkylation or the Sonogashira coupling for the synthesis of some natural products and useful chemicals 5. A variety of effective catalytic systems including amino‐alcohol–Zn,6 imino‐alcohol–Zn,7 hydroxyl‐carboxyamide–Zn,8 proline‐derived dinuclear Zn,4i bisoxazolidine–Zn,4j 1,1′‐bi‐2‐naphthol (BINOL)–Ti,9 bisphosphine–Cu I ,10 sulfonamide‐alcohol–Ti,11 and bis(oxazolinyl)phenyl–Ru4q have been developed for the addition of trimethylsilylacetylene to aldehydes. In particular, by using catalytic systems such as Trost’s proline‐derived dinuclear Zn,4i Wolf’s bisoxazolidine–Zn,4j Pu’s BINOL–Ti,9b Wang’s sulfonamide alcohol–Ti,11 and Nishiyama’s bis(oxazolinyl)‐phenyl–Ru,4q excellent enantioselectivity (>90 % enantiomeric excess ( ee )) can be achieved in the addition of trimethylsilylacetylene to aldehydes.…”

Highly Enantioselective Addition of Trimethylsilylacetylene to Aldehydes Catalyzed by a Zinc–Amino‐Alcohol Complex

“…[5] A variety of effective catalytic systems including amino-alcohol-Zn, [6] iminoalcohol-Zn, [7] hydroxyl-carboxyamide-Zn, [8] proline-derived dinuclear Zn, [4i] bisoxazolidine-Zn, [4j] 1,1'-bi-2-naphthol (BINOL)-Ti, [9] bisphosphine-Cu I , [10] sulfonamide-alcoholTi, [11] and bis(oxazolinyl)phenyl-Ru [4q] have been developed for the addition of trimethylsilylacetylene to aldehydes. In particular, by using catalytic systems such as Trosts prolinederived dinuclear Zn, [4i] Wolfs bisoxazolidine-Zn, [4j] Pus BINOL-Ti, [9b] Wangs sulfonamide alcohol-Ti, [11] and Nishiyamas bis(oxazolinyl)-phenyl-Ru, [4q] excellent enantioselectivity (> 90 % enantiomeric excess (ee)) can be achieved in the addition of trimethylsilylacetylene to aldehydes.…”

Enantioselective Zinc‐Mediated Conjugate Addition of Terminal Alkynes to Enones

“…[12] Herein, we describe the first zinc-mediated conjugate alkynylation of enones by employing catalytic amounts of a chiral inducer, which is promoted by diethylzinc. Previously, our group has described the dialkylzinc-mediated addition of terminal alkynes to aldehydes [13] and imines [14] in the presence of catalytic amounts of hydroxyamides and BINOLtype ligands, respectively.…”

“…For the optimization of the conditions, we studied the reaction between enone 1 a (R 1 = Me, R 2 = Ph) and phenylacetylene (2 a) by using different binaphthol ligands ( Table 1). The starting conditions were similar to those used by us for the alkynylation of aldehydes: [13] the reactive species were generated by heating the chiral ligand, phenylacetylene, and dimethylzinc in toluene at 70 8C for 1.5 h, followed by addition of the electrophile at the same temperature. Following this protocol, different binaphthol-type ligands were screened (entries 1-10), the best result being obtained with the vaulted ligand (R)-VANOL (L9, (R)-3,3'-Diphenyl-2,2'-bi-1-naphthalol).…”