3-Acyloxy-1,4-enyne: A new five-carbon synthon for rhodium-catalyzed [5 + 2] cycloadditions

Abstract

Seven-membered rings are ubiquitous in natural products and pharmaceutical agents and their syntheses continue to stimulate the development of novel synthetic methods. The (5+2) cycloaddition is one of the most efficient ways to access seven-membered rings since the 2-carbon components (alkenes, alkynes, or allenes) are readily available. Prior to our study, however, there was only one type of transition metal-catalyzed (5+2) cycloaddition: the reaction between vinylcyclopropanes and alkenes, alkynes, or allenes. We recently developed a new type of transition metal-catalyzed (5+2) cycloaddition, where the 5-carbon building block is 3-acyloxy-1,4-enyne (ACE). Our recent progress on Rh-catalyzed intra- and intermolecular (5+2) cycloadditions of ACEs and alkynes is summarized in this article. Using chiral propargylic esters, bicyclic products were prepared in high optical purity by the intramolecular (5+2) cycloadditions. Monocyclic seven-membered rings were synthesized by intermolecular (5+2) cycloaddition of ACEs and alkynes. Kinetic studies indicated that the rate of this intermolecular cycloaddition was significantly accelerated when the acetate was replaced by dimethylaminobenzoate. DFT calculations suggested that novel metallacycles were generated by a Rh-promoted oxidative cycloaddition of 1,4-enynes accompanied by a 1,2-acyloxy migration of propargylic esters.

Synthesis of Carbazoles and Carbazole-Containing Heterocycles via Rhodium-Catalyzed Tandem Carbonylative Benzannulations

“…Previously, we and others have demonstrated that 3-acyloxy-1,4-enyne 38 can serve as the five-carbon component in Rh-catalyzed [5 + 1] cycloaddition, and we also extended it to [5 + 2] cycloaddition , as shown in Scheme A. DFT calculations suggested a rhodium-mediated concerted oxidative cyclization accompanied by 1,2-acyloxy migration as shown in 39 for the formation of metallacycle 40 from ester 38 .…”

A Comparison between the Cycloadditions of Allenyl- and Vinyl-Cyclopentanes Using Density Functional Theory and GRRM Program

“…Small cycloalkanes are critical for organic synthesis in medicinal chemistry, [4][5][6] and transition metal catalysts are sometimes utilized to obtain functional molecules from cycloalkanes as the starting point. Rhodium (I) catalyzes the cycloadditions [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] of vinyl-or allenylcycloalkanes. Reactants containing 3-membered, 4-membered, and 5-membered rings have been reported.…”

Synthesis of substituted tropones by sequential Rh-catalyzed [5+2] cycloaddition and elimination

“…13 The high degree of unsaturation and the enol ester functionality in cycloaddition product 9 are ideally set up for the synthesis of substituted tropone 10 . We herein report our efforts along this direction for the first time.…”