Polarity Matching of Radical Trapping: High Yielding 3‐exo and 4‐exo Cyclizations

Abstract

A catalyzed synthesis of cyclopropanes and cyclobutanes via radical chemistry is described. The method that generally proceeds in high yields uses epoxides as radical precursors and titanocene(III) complexes as the electron transfer catalysts (see scheme). The key to the success of the transformation is constituted by the chemoselectivity of radical reduction. Electrophilic enol radicals generated through cyclization are reduced rapidly whereas their precursors, nucleophilic alkyl radicals, remain unaffected.

Structural Diversity from the Transannular Cyclizations of Natural Germacrone and Epoxy Derivatives: A Theoretical–Experimental Study

“…It should be noted that compounds 26 and 27 were formed as a result of a radical 4-exotrig,3-exo-trig domino process. Individual 3-exo-trig [35] or 4exo-trig [36] cyclizations have been reported, but as far as we know, there are no precedents for a transformation involving the consecutive generation of a four-and then a three-membered cycle.…”

New Advances in Titanium-Mediated Free Radical Reactions

“…The use of Cp 2 TiCl (in stoichiometric or catalytic amounts) allowed to promote the synthesis of natural products by the construction of three- to six- and eight-membered carbocycles in good to excellent yields [ 115 , 116 , 117 , 118 , 119 , 120 ]. Small ring 3- exo and 4- exo cyclizations were achieved by nucleophilic intramolecular radical addition to aldehydes and ketones [ 117 ] and natural products, like (E)- endo -bergamoten-12-oic acids [ 115 ] or carbacephams, are significant examples of synthetic applications ( Scheme 39 ) [ 121 , 122 , 123 , 124 , 125 ].…”

Nickel-Catalyzed Reductive Electrophilic Ring-Opening of Benzofurans with Alkyl Halides

“…The challenge of realizing electrophilic ring-opening reactions lies in overturning the intrinsic electrophilic nature of ring molecules. To date, the most successful examples of catalytic electrophilic ring-opening reactions are limited to epoxides [2][3][4][5][6][7][8][9][10][11][12][13][14] with a few exceptions of other small, strained rings, such as aziridines, [15][16][17][18][19] oxetanes, 20 azetidinones, 21,22 cyclobutanones, 23 and cyclobutanone oxime esters. 24 Therefore, it is highly desirable to develop a new methodology to allow electrophilic ring-opening reactions to go beyond the small ring system.…”