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Tropone and related compounds in the troponoid family were initially well-known for having nonbenzenoid aromaticity.1 Since the pioneering work of Tetsuo Nozoe in the 1930s,2 interest on such a theoretical aspect has stimulated extensive studies of the synthesis, structure, and reactivity of troponoids,3 which has continued until the present time. Some noteworthy examples in recent years include the following: the phosphoramidite-palladium complex catalyzed asymmetric [6+3] cycloaddition with trimethylenemethane and applications to welwitindolinone core synthesis by Trost, et al.;4a,b From the synthetic point of view, Diels-Alder reactions of tropone can provide direct access to bicyclo[3.2.2] ring structures, which could be further elaborated into more complex molecular architectures through selective manipulation of their pre-existing functional groups. Under thermal conditions, tropone, as a diene, participates in not only normal-Diels-Alder reactions with electron-deficient dienophiles 5 but also inverse-electron-demand Diels-Alder reactions with electron-rich dienophiles.6 , 7 However, neither the Lewis acid catalyzed nor asymmetric version has been studied.As a continuation of our interest in developing Lewis acid catalyzed reactions, especially their asymmetric versions, 8 we initiated the current investigation of the tropone Diels-Alder reaction, which could constitute a rare example of all-carbon based catalytic enantioselective inverse-electron-demand Diels-Alder reactions. To the best of our knowledge, the only previous case on such a scenario was the study on 2-pyrone Diels-Alder chemistry by Markó, et al. and Posner, et al. 9 We began the trials with tris(pentafluoro)phenylborane10 , 11 to catalyze this Diels-Alder reaction between tropone and ethyl vinyl ether. Gratifyingly, desired [4+2] adducts were obtained as a mixture of regio-and diastereoisomers under ambient temperature and pressure, while the previous report6a required high temperature and ultrahigh pressure in the absence of a Lewis acid catalyst. The scope of this reaction was briefly explored as shown in Table 1 To improve the reaction's efficiency and selectivity, a screening of various typical achiral and chiral Lewis acid catalysts was undertaken for the reaction between tropone and ethyl vinyl ether. However, we soon realized that most of these catalysts were ineffective, with no conversion of tropone and significant decomposition of ethyl vinyl ether, perhaps through either cationic or coordinative polymerization. Thus, the important role of tris(pentafluoro) phenylborane as an active, yet mild Lewis acid catalyst is noteworthy. 11 Since ketene acetals are considerably more electron-rich than vinyl ethers, they could be more likely to participate in the inverse-electron-demand Diels-Alder reaction with tropone. Indeed, the reaction between ketene diethyl acetal and tropone catalyzed by tris(pentafluoro)phenylborane can proceed at 0 °C to give the Diels-Alder adduct ( Lewis acid catalysts is of great mechanistic interest to us...

Platensimycin (1) (Scheme 1) is a novel antibiotic lead compound recently discovered by Merck scientists from a strain of Streptomyces platensis. 1a,b The potential medicinal applications 1c,d and challenging structure motif, especially the cage-like tetracyclic core with several stereogenic centers, made this compound very attractive as a target for chemical synthesis. To this end, total synthesis of its racemic form was first reported by Nicolaou and co-workers, 2a and later they also reported corresponding asymmetric versions. 2b More recently, two other routes to the tetracyclic core structure (±)-9 2c,d and synthesis of a related structure 2e have been reported. Whereas these reported routes all utilized intramolecular etherification reactions 2a between the alcohol motifs and the alkene parts as key steps, an alternative intramolecular Robinson annulation approach seems to be more straightforward. Herein, we describe our efforts in the enantioselective synthesis of the key cage-like tetracyclic core structure of platensimycin.

Herein we disclose a new catalytic asymmetric approach for the synthesis of chiral α-amino ketones, which is particularly useful for the less accessible acyclic α-tertiary cases. By a protonation−amination sequence, our approach represents a rare asymmetric H−heteroatom bond insertion by αcarbonyl sulfonium ylides, an attractive surrogate of diazocarbonyls. The mild intermolecular C−N bond formation was catalyzed by chiral phosphoric acids with excellent efficiency and enantioselectivity. The products are precursors to other important chiral amine derivatives, including drug molecules and chiral ligands. The enantioselectivity was controlled by dynamic kinetic resolution in the amination step, rather than the initial protonation. This process opens up a new platform for the development of other related insertion reactions.