The radical-mediated carboazidation of terminal alkenes using electrophilic alkanesulfonyl azides is reported. A single reagent delivers the necessary electrophilic alkyl radical as well as the azido group, and good yields are obtained by using a moderate excess of the carboazidating reagent (1.5-2 equiv). Interestingly, in addition to the starting sulfonyl azide, this method requires only the use of a radical initiator, di-tert-butyldiazene. In terms of atom economy, this azide transfer reaction is close to ideal, as SO2 (1 equiv) is the only side product. The synthetic potential of this process has been demonstrated by a formal synthesis of the alkaloid lepadiformine C.
Boron derivatives are becoming key reagents in radical chemistry. Here, we describe reactions where an organoboron derivative is used as a radical initiator, a chain-transfer reagent, and a radical precursor. For instance, B-alkylcatecholboranes, easily prepared by hydroboration of alkenes, represent a very efficient source of primary, secondary, and tertiary alkyl radicals. Their very high sensitivity toward oxygen-and heteroatom-centered radicals makes them particularly attractive for the development of radical chain processes such as conjugate addition, allylation, alkenylation, and alkynylation. Boron derivatives have also been used to develop an attractive new procedure for the reduction of radicals with alcohols and water. The selected examples presented here demonstrate that boron-containing reagents can efficiently replace tin derivatives in a wide range of radical reactions.
A novel reaction for the introduction of an azide moiety by means of a mild radical process is currently under development. Sulfonyl azides are suitable azidating agents for nucleophilic radicals, such as secondary and tertiary alkyl radicals. More electrophilic radicals, such as enolate radicals, do not react with sulfonyl azides. This feature allowed the development of efficient intra- and intermolecular carboazidations of olefins. Due to the versatility of the azido group, this reaction has an important synthetic potential, as already demonstrated by the preparation of the core of several alkaloids, particularly those containing an amino-substituted quaternary carbon center, such as FR901483.
A procedure for one-pot intermolecular radical addition of 2-iodoesters to terminal alkenes followed by azidation of the radical adduct has been developed. This sequential reaction represents an alkene carboazidation process. Its efficacy is demonstrated by the two-step preparation of various lactams such as pyrrolidinones, pyrrolizidinones, and indolizidinones. An easy access to spirolactams bearing an amino-substituted quaternary carbon center is also described. These compounds are important building blocks for the synthesis of numerous alkaloids such as, for instance, FR901483.
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
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