Asymmetric Synthesis of 3,4-Dihydrocoumarins by Rhodium-Catalyzed Reaction of 3-(2-Hydroxyphenyl)cyclobutanones

摘要

Significant advances have been made over the past decade in the field of activation of carbon—carbon single bonds by means of transition metal catalysis. Now a variety of catalytic processes are available for organic transformations including cross-coupling and ring-expansion reactions. We recently developed the rhodium-catalyzed reaction of boron-substituted cyclobutanones forming 1-indanones. Enantioselectivities up to 95% ee were observed during the sequence of intramolecular addition/ring-opening reactions when stereogenic quaternary carbon centers arose at the benzylic position. It was also found that rhodium catalysts promote the ring-opening reaction of cyclobutanones with phenols to form ester linkages via inter- and intramolecular pathways. In this paper, we describe an asymmetric synthesis of 3,4-dihydrocoumarins by way of a highly enantioselective carbon—carbon bond cleavage. Deuterium-labeling experiments led to the development of a new cascade reaction involving 1,4-rhodium shift and intermolecular conjugate addition.rnWhen 3-(2-hydroxyphenyl)cyclobutanone (1a) was treated with a catalytic amount of a rhodium(Ⅰ) catalyst, prepared in situ from [Rh(OH)(cod)]_2 (7 mol %) and (R)-SEGPHOS (16 mol %), in toluene at room temperature for 19 h, 4-methyl-3,4-dihydrocoumarin (2a) was produced in 77% isolated yield (Scheme I). Only one enantiomer was observed by chiral HPLC analysis. The absolute configuration was assigned to be S by comparison with the reported optical rotation. BINAP and Tol-BINAP were also effective as the chiral ligands, both giving 96% ee. We propose a possible mechanism which consists of (i) generation of rhodium aryloxide 3, (ii) addition to the carbonyl group forming rhodium cyclobu-tanolate 4, (iii) ring opening of the cyclobutane skeleton by β-carbon elimination generating 5, which is the enantiodifferen-tiating step, and (iv) protonolysis affording the dihydrocoumarin 2a, as we proposed recently.