Strategy of total synthesis based on the use of Rh-catalyzed stereoselective 1,4-addition

Abstract

In 1998, Hayashi and Miyaura reported the first asymmetric conjugate addition of aryl- and alkenyl-boronic acids to α,β-unsaturated ketones using chiral rhodium complexes as catalysts. During the last decade, this reaction has been developed quickly and the enantioselectivity was significantly improved with the emergence of new phosphine ligands. In addition to the methodological work, this reaction was applied as a key step in the total synthesis of natural compounds. The purpose of this paper focuses on examples of the use of this reaction to prepare elaborated chiral molecules with high diastereoselectivies and/or enantioselectivities.

Chiral Diene Ligands in Asymmetric Catalysis

“…The enantioselective formation of a C–C bond via the transition-metal-catalyzed asymmetric addition of organoboron reagents to acceptors (including CC, CO, CN, etc.) is known as one of the most useful methods in organic synthesis and has developed rapidly in recent years. − In addition to the traditional phosphorus and nitrogen coordination ligands, a variety of chiral diene ligands have been developed and applied in this field. In this section, asymmetric reactions catalyzed by chiral diene–transition metal complexes are summarized.…”

“…β-Pyrazolyl acrylate esters 120 were also reported to undergo the rhodium-catalyzed asymmetric addition of arylboronic acids with ligand L4a to produce chiral N -alkylpyrazole products 121 (Scheme c) . This asymmetric transformation has been applied to the synthesis of an intermediate of (−)-indatraline …”

“…180 This asymmetric transformation has been applied to the synthesis of an intermediate of (−)-indatraline. 111 o-Quinone methide, which is classified as an α,β-unsaturated ketone, is known to be a very reactive acceptor for conjugate addition reactions, although the low availability of isolable quinone methides is a serious drawback. A new strategy has been developed where o-quinone methides are generated in situ under the conditions of rhodium-catalyzed asymmetric conjugate addition (Scheme 33).…”

Development of ChiralC2-SymmetricN-Heterocyclic Carbene Rh(I) Catalysts through Control of Their Steric Properties

“…Afterward, chiral Rh­(I) complexes 4a – e were applied as precatalysts in another reference reaction, the asymmetric 1,2-addition of phenylboronic acid to 1-naphthaldehyde (Table ). Indeed, the enantioselective addition of aryl nucleophiles to aromatic aldehydes is a well-established route to synthesize chiral diarylmethanols which are essential building blocks for the synthesis of various biologically active and pharmacy relevant compounds . Many antihistamines, antiarrhythmic, and therapeutic agents feature chiral diarylmethanol and diaryl carbinol derivatives as fundamental structural units.…”

Chiral N-aryl tert-butanesulfinamide-olefin ligands for rhodium-catalyzed asymmetric 1,4-addition of aryl boronic acids to cyclic enones

“…28 As we know, sulfinamide-olefin compounds are recently used as chiral ligand in highly enantioselective rhodium-catalyzed asymmetric 1,4-addition reaction of arylboronic acids to ,-unsaturated carbonyl compounds, [29][30] which has extensive applications in medicinal synthesis and natural synthesis, 31 and has achieved great progress. [32][33][34][35][36][37][38][39] Furthermore, the C-N coupling reaction products are seldom directly used as chiral ligands.…”