Asymmetric copper-catalyzed conjugate additions of organometallic reagents in the syntheses of natural compounds and pharmaceuticals

Abstract

Stereoselective copper-catalyzed conjugate additions of organometallic reagents serve as a versatile tool in the total syntheses of diverse natural compounds and pharmaceutical agents.

Polymer-Supported Chiral Heterogeneous Copper Catalyst for Asymmetric Conjugate Addition of Ketones and Imines under Batch and Flow

“…23,24 Organometallic reagents provide a powerful way of introducing alkyl groups to various substrates, acting as a complementary method to other existing procedures. 18 Chiral heterogeneous catalysts have several advantages over homogeneous ones. First, they are easier to handle and the expensive organic ligands can be readily separated and reused.…”

“…Furthermore, a broad range of substrates including α,β-unsaturated ketones, esters, amides, imines, , and nitroalkenes, in combination with a diverse set of ligands, were developed. This chemistry has been successfully applied in the synthesis of pharmaceuticals, natural products, and other important optically active compounds. − …”

“…In contrast with these advances, reports involving chiral heterogeneous catalysts in ACA reactions were rather limited. Even though excellent pioneering work on Rh-catalyzed Michael addition of organoboron reagents has been reported by Kobayashi, , Hayashi, and Uozumi, cases employing sensitive organometallic reagents remain a key challenge. , Organometallic reagents provide a powerful way of introducing alkyl groups to various substrates, acting as a complementary method to other existing procedures . Chiral heterogeneous catalysts have several advantages over homogeneous ones.…”

Crown Ether-Derived Chiral BINOL: Enantioselective Michael Addition of Alkenyl Boronic Acids to α,β-Unsaturated Ketones

“…The studies on organometallic reagents’ asymmetric conjugate additions of α,β-unsaturated carbonyl compounds have engendered a few reliable catalytic methods . The most outstanding approach among them is the Rh-catalyzed asymmetric conjugate addition of organoboronic acid to α,β-unsaturated carbonyl substrates. , Palladium and copper complexes are also effective catalysts. To avoid the use of precious chiral metal catalysts, endeavors on employing organocatalysts, such as binaphthol (BINOL) derivatives, led to the advent of non-metal catalytic methods.…”

Concise Total Synthesis of Peyssonnoside A

“…The synthesis can be optimized further by an enantioselective approach to peyssonnosol ( 3 , Scheme ) with the asymmetric 1,4-addition step to 11 as a key challenge. In general, this chemistry is well-developed, yet 2-methyl-2-cyclopenten-1-one ( 11 ) turned out to be a quite challenging substrate, for which it is difficult to achieve high enantioselectivity. − Quinkert and co-workers reported in 1992 that isopropenyl lithium can be asymmetrically added to 11 in the presence of excess of O -methyl- d -prolinol ( SMP ) affording the desired ( R )-enantiomer of 27 with 60–89% ee, which was used in a (+)-confertin synthesis . This method was adopted for our synthesis.…”