A novel and practical procedure for the preparation of 3-unsubstituted indolizines by 1,3-dipolar cycloaddition was developed. The requisite pyridinium N-methylides were generated simply from the corresponding N-(carboxymethyl)pyridinium halides. In the presence of MnO 2 , electron-deficient alkenes, instead of alkynes or vinyl bromides, were used successfully as dipolarophiles. This general method features cheap reagents, simple workup procedure and gives the products in moderate to high yields (57-92%).In the family of indolizines, 3-unsubstituted indolizine is especially important because the highest electronic population in the p-excessive heterocycle focuses on C-3, 1 which allows many electrophilic substitutions. 2 Their derivatives are also key intermediates for the synthesis of some theoretically and practically interesting biindolizines, 3 cyclophones 4 and cyclozines, 5 and biologically important alkaloids. 6 Significant efforts have been made to develop methods for the preparation of 3-unsubstituted indolizines in the past decades. Unfortunately, most of them suffered from tedious procedures and very low yields. 7 Although the Tschitschibabin reaction 8 has been widely used as a general method for this purpose, it requires precursors with special structures. However, the method using 1,3-dipolar cycloaddition of pyridinium N-methylides with electron-deficient alkynes or alkenes attracted our attention due to its flexibility and convenience. 6,9 Two precursors have been employed to generate the requisite pyridinium N-methylides. One is N-(trimethylsilylmethyl)pyridinium trifluromethanesulfonate 9a and the other is N-[a-(benzotriazol-1-yl)methyl]pyridinium halide. 9b In these procedures, dialkyl acetylenedicarboxylates are usually used as dipolarophiles. When electron-deficient alkenes were used for the same purpose, their structures should be modified into corresponding vinyl bromides. 9bHowever, literature survey showed that N-(carboxymethyl)pyridinium halides (C 5 H 5 N + CH 2 CO 2 H X -) have served as precursors of pyridinium N-methylides. 10 Two possible N-methylides, C 5 H 5 N + CH 2 -and C 5 H 5 N + CH -CO 2 H, were proposed and usually led to decarboxylative products. It is surprising to note that this method has never been used in 1,3-dipolar cycloaddition. When we tried to heat a mixture of N-(carboxymethyl)pyridinium chloride (1a), dimethyl acetylenedicarboxylate (DMAD) and triethylamine in toluene at 90°C for 2 hours, dimethyl indolizine-1,2-dicarboxylate (2a) was obtained smoothly in 82% yield, whose structure was assigned by IR, 1 H NMR, and mass spectra. Under similar conditions, N-(carboxymethyl)isoquinolinium chloride (1b) gave dimethyl 7,8-benzoindolizine-1,2-dicarboxylate (2b) in 77% yield (Scheme 1). These exciting results proved that the derivatives of N-(carboxymethyl)pyridinium halides can be successfully employed as very good precursors of pyridinium N-methylides in the 1,3-dipolar cycloaddition for the preparation of 3-unsubstituted indolizines. Scheme 1Recently, we have reporte...

The first total synthesis of (-)-lannotinidine B, a unique tetracyclic constitutent of Lycopodium annotinum, has been accomplished in 10 steps with 23% overall yield. The completed short and efficient synthesis is characterized with three highly chemo- and/or stereoselective reductive-amination steps to furnish the desired trans-fused 6/6 bicycle and the aza seven-membered ring system, and a direct intramolecular acyloin condensation to deliver the cyclopentanone moiety, as well as successful application of a protecting group-free strategy and an optimal redox order.

A new enantioselective total synthesis of phlegmarine-type Lycopodium alkaloid lycoposerramine-Z (1) has been accomplished, using one-pot chemoselective sequential additions of two different Grignard reagents to the bis-Weinreb-amide intermediate and an efficient construction of the fully fuctionalized cyclohexanone intermediate with a chiral phosphoric acid catalyzed enantioselective intramolecular Michael addition.

A novel approach to synthesize pyrrolo[1,2-a]quinoxalines was developed successfully by 1,3-dipolar cycloaddition of a quinoxalinium N-ylide to alkenes in the presence of MnO 2 under very convenient conditions and with moderate yields (40^52%).