Radical Carboazidation of Alkenes: An Efficient Tool for the Preparation of Pyrrolidinone Derivatives

Abstract

The use of free radical reactions in multistep synthesis has steadily increased over the last years, mainly because of their compatibility with a large number of functional groups and their high potential for performing sequential transformations. [1] Recently, we developed a novel method that allows the efficient formation of carbon±nitrogen bonds by reaction of radicals with sulfonyl azides. [2,3] Since sulfonyl azides possess an electrophilic character, this azidation process is particularly efficient with nucleophilic radicals and does not occur with ambiphilic or electrophilic radicals. For instance, the cyclization depicted in Scheme 1 can be performed by mixing all the reagents at once under relatively concentrated conditions (0.5 m substrate) without the formation of even traces of noncyclized products.This observation let us speculate that the reaction could also be accomplished in intermolecular processes. Here we report our first results on the intermolecular addition of radicals to unactivated alkenes followed by azidation. This reaction sequence represents a formal carboazidation of alkenes, and it is the key process for an efficient threecomponent synthesis of pyrrolidinone, pyrrolizidinone, and indolizidinone derivatives.In a first series of experiments, we tested the feasibility of the reaction starting from terminal alkenes and different radical precursors that are known to be efficient in radical atom or group transfer reactions (Scheme 2, see also Table 1). [4] A one-pot procedure similar to that used for intramolecular reactions gave promising results: The radical precursors are treated with phenylsulfonyl azide (3 equiv), COMMUNICATIONS 3460The procedure for the asymmetric alder±ene reaction of 1 b catalyzed by rhodium (2 b): [4] In a dried Schlenk tube, [{Rh(cod)Cl} 2 ] (4.9 mg, 0.01 mmol) and (S)-BINAP (13.8 mg, 0.022 mmol) were dissolved in freshly distilled 1,2-dichloroethane (2 mL), then freshly prepared 1 b (37.2 mg, 0.2 mmol) was added to the solution at room temperature under nitrogen. After the mixture had been stirred for 1 min, AgSbF 6 (0.04 mmol) was added, and the reaction was complete within 5 min. The reaction mixture was directly subjected to column chromatography. Compound 2 b (35.8 mg, 96 % yield, > 99.9 % ee) was obtained. The ee value was determined by GC with chiral select 1000 at 150 8C. [a] D ¼ 23.85 (c ¼ 0.5, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): d ¼ 7.33±7.29 (m, 2 H), 7.22±7.18 (m, 1 H), 7.12±7.10 (m, 2 H), 6.24( s, 1 H), 5.70±5.65 (m, 1 H), 5.2±5.16 (m, 2 H), 4.77 (d, J ¼ 14.0 Hz, 1 H), 4.64 (d, J ¼ 14.0 Hz, 1 H), 4.15 (t, J ¼ 7.7 Hz, 1 H), 3.60±3.48 ppm (m, 2 H); 13 C NMR (90 MHz, CDCl 3 ): d ¼

Free-Radical Azidation with γ-15N-Labeled Phenylsulfonyl Azide

“…[1][2][3][4][5][6][7] The reaction has been shown to proceed smoothly using both phenylsulfonyl azide (1) and ethanesulfonyl azide (2) with great success. Free-radical azidation has also been explored in systems where diastereocontrol was at issue.…”

“…The reaction mixture was worked up in the normal manner by extraction providing a 96% yield of g-15 N phenylsulfonyl azide (Scheme 2). Scheme 2 Preparation of g-15 N-labeled phenyl sulfonyl azide (1) Free-radical azidation was performed using a variety of substrates in order to determine the generality of the reaction mechanism. A free-radical azidation reaction was performed by slow infusion of Barton ester 3 into a solution of 1 under photolysis conditions.…”

Boron — A Key Element in Radical Reactions

“…Therefore, it has to be used in stoichiometric amount. Recently, we have developed a radical carboazidation [9][10][11][12] reaction that has found numerous applications for alkaloid synthesis [13][14][15]. The chain process requires the transformation of an arylsulfonyl radical into an alkyl radical.…”

Radical azidation reactions and their application in the synthesis of alkaloids

“…This threecomponent sequence represents a formal carboazidation of alkenes (Scheme 2) [12,13]. When followed by a reduction/lactamization sequence, this reaction gives direct access to pyrrolizidinones and indolizidinones.…”