The indolizidine structural motif forms the core of many natural products with pharmacological relevance, such as indolizidine [1] and phenanthroindolizidine [2] alkaloids (septicine (1), antofine (2), and tylophorine (3)), camptothecin (4, CPT), [3] and aromathecin alkaloids [4] (rosettacin (5) and 22-hydroxyacuminatine (6)). While a number of synthetic methods for the construction of these scaffolds have been reported, [1][2][3][4] the development of conceptually different synthetic approaches is still of great interest.The rhodium(III)-catalyzed oxidative CÀH activation has received significant interest in recent years because of its high efficiency, selectivity, and functional-group tolerance.[5] Generally, these reactions require stoichiometric amounts of external oxidants [Eq. (1)], [6] thus resulting in the generation of undesired waste. Recently, Fagnou et al. reported an oxidizing-directing-group strategy [7] for the rhodium-catalyzed synthesis of isoquinolones by intermolecular CÀH activation of N-methoxy/pivaloyloxy benzamides and alkynes [Eq. (2); Piv = pivaloyl], [8] which not only obviates the need for an external oxidant, but also increases the reactivity and selectivity under mild conditions. During our investigation of the reactivity of a-oximino carbenoids, [9] we observed facile intramolecular N À O insertion of oxime ether moieties, which results in the formation of 2-alkoxy/aryloxy-2H-azirines.[10]The cleavage of the N À O bond plays an important role in Fagnous rhodium-catalyzed intermolecular CÀH activation of N-methoxy/pivaloyloxy benzamides and in our NÀO insertion of a-oximino carbenes. Based on this observation, we became interested in the intramolecular reaction of alkyne-tethered hydroxamic esters [Eq. (3)]. The successful development of this reaction would lead to a general and facile synthesis of hydroxyalkyl-substituted isoquinolone/2-pyridone derivatives, which could be readily transformed into indolizidine scaffolds. Herein, we wish to report these results, and the total synthesis of (AE)-antofine, (AE)-septicine, (AE)-tylophorine, and rosettacin based on rhodium(III)-catalyzed C À H bond functionalization as the key step.Our synthetic attempts began with the reaction of 7 a by employing Fagnous intermolecular reaction conditions [7] (Table 1, entries 1 and 2). We found that treatment of 7 a with [(Cp*RhCl 2 ) 2 ] (2.5 mol %) and CsOAc (30 mol %) in MeOH at 60 8C gave isoquinolones 8 a and 8 a' (29:1) in 98 % yield in 0.2 hours (Table 1, entry 1). Similar results were obtained with a reduced catalyst loading (0.5 mol %) and reaction temperature, however, a longer reaction time was required in this case (12 h; Table 1, entry 2). Improved

Push-pull alkenes, which bear electron-donating and -accepting group(s) at both termini of a C═C double bond, respectively, are of interest not only for their unique electronic properties but also for their importance as versatile building blocks in organic synthesis. In the world of ketene acetals having the push-pull alkene skeleton, ketene N,S-acetal is most likely the biggest family according to the number and types of these compounds. The first ketene N,S-acetal compound was reported in 1956. As a cyclic ketene N,S-acetal compound, nithiazine, the first lead structure of neonicotinoid insecticides, was reported in 1978. The characteristics of ketene N,S-acetals, which have the structural feature of ketene S,S-acetals and enaminones, make them versatile and easy to use, especially in cyclization and multicomponent reactions for the synthesis of various heterocyclic systems and related natural products. There has been an increasing wealth of information about the synthesis and synthetic applications of ketene N,S-acetals, especially, in recent years. This review provides comprehensive knowledge on the chemistry of ketene N,S-acetals.

A new strategy, the 1,3-carbothiolation/aromatization, for the synthesis of functionalized (trifluoromethyl)arenes has been developed that enables the regioselective introduction of two different functional groups onto an "aromatic ring" in the meta-position to each other in a single step.

A new strategy for the construction of the compounds with two different heterocycles, linked by a C(2)-tether via a domino process involving [5 + 1] annulation, ring-opening, and subsequent double isocyanide cyclization, from the reaction of ethyl isocyanoacetate with divinyl ketones (DVKs) has been developed. The chemoselective fragmentation of the cyclohexanone intermediate is the key for the formation of not only the C(2)-tether but also the two different heterocycles.

Roaming the range: The title reaction tolerates a wide range of substituents on the resulting pyridine ring using mild reaction conditions (see scheme; esp=α,α,α′,α′‐tetramethyl‐1,3‐benzenedipropionic acid). The formation of the key intermediate is catalyst‐controlled, and subsequent cyclization and oxidation affords pyridines in excellent yields. The method has been used for the efficient synthesis of polyarylpyridines.