Rhodium(I)‐Catalyzed Carboacylation/Aromatization Cascade Initiated by Regioselective C−C Activation of Benzocyclobutenones

Abstract

Described here is the first example of a rhodium-catalyzed carboacylation/aromatization cascade of a C=O bond by C-C activation. In this transformation, a reactive rhodaindanone complex is regioselectively generated and adds across a C=O bond with subsequent elimination, thus providing a unique strategy to access a multisubstituted benzofuran scaffold. A diverse range of benzofuran analogues were obtained in good yields. Mechanistic studies show a tricyclic lactone was a viable intermediate. Application of this methodology to the total synthesis of C13-deOH-viniferifuran and C13-deOH-diptoindonesin G was achieved.

Rhodium(I)‐Catalyzed Carboacylation/Aromatization Cascade Initiated by Regioselective C−C Activation of Benzocyclobutenones

“…[7] To our delight, 2a was successfully isolated in 10 % yield. [11] An optimization of solvents revealed that ethereal solvents are preferred (entries [10][11][12][13][14], whereas DCE drastically limited conversion to 20 %and less than 10 %yield upon isolation. Several cationic rhodium pre-catalysts were screened and both conversions and yields were dramatically increased (entries 2-4).…”

“…Heteroaryl-bearing ketone substrates were also found to be suitable substrates (entries [10][11][12][13]. Sterically hindered ortho-substituted phenyl ketones 1h and 1i were prepared and found to undergo the cascade transformation with even better efficiency, thus providing 2h and 2i, respectively,a nd in 90 %y ields (entries 8a nd 9).…”

“…Heteroaryl-bearing ketone substrates were also found to be suitable substrates (entries [10][11][12][13]. [13] Given the broad substrate scope,w es ought to demonstrate our reaction in am uch more complex setting.T he substrate 1x was prepared through coupling with known 2bromo-dihydrocholesterol (see the Supporting Information for details,[ Eq. We hypothesize that amideand N-containing heteroaryl rings were challenging substrates primarily because of 1) the coordinating ability of amide group with transition metals,and 2) the competing C À Nbond cleavage under rhodium catalysis, [12] which may alter the reaction pathway.Inaddition to aryl ketones,the alkyl ketone substrate 1o also served as suitable substrates (entry 15).…”

“…Sterically hindered ortho-substituted phenyl ketones 1h and 1i were prepared and found to undergo the cascade transformation with even better efficiency, thus providing 2h and 2i, respectively,a nd in 90 %y ields (entries 8a nd 9). Heteroaryl-bearing ketone substrates were also found to be suitable substrates (entries [10][11][12][13]. Labile furan (2k), thiophene (2l), and catechol acetal (2m)w ere compatible with the reaction conditions,p resumably because of the pH and redox neutral conditions.W ea lso demonstrated the compatibility of the amide-containing substrates 1n (entry 14), thus providing 2n, albeit with moderate conversion as well as yield (63 %based on recovered starting materials).…”

“…We obtained multiple single-crystal structures of several products to unambiguously verify the structures (summarized in Table 2). [13] Given the broad substrate scope,w es ought to demonstrate our reaction in am uch more complex setting.T he substrate 1x was prepared through coupling with known 2bromo-dihydrocholesterol (see the Supporting Information for details,[ Eq. (1)]).…”