Double catalytic enantioselective transformations are powerful synthetic methods that can facilitate the construction of stereochemically complex molecules in a single operation. In addition to generating two or more stereocentres in a single reaction, multiple asymmetric reactions also impart increased enantiomeric excess to the final product in comparison with the analogous single transformation. Furthermore, multiple asymmetric operations have the potential to independently construct several stereocentres at remote points within the same molecular scaffold, rather than relying on pre-existing chiral centres that are proximal to the reactive site. Despite the inherent benefits of multiple catalytic enantioselective reactions, their application to natural product total synthesis remains largely underutilized. Here we report the use of a double stereoablative enantioselective alkylation reaction in a concise synthesis of the marine diterpenoid (-)-cyanthiwigin F (ref. 8). By employing a technique for independent, selective formation of two stereocentres in a single stereoconvergent operation, we demonstrate that a complicated mixture of racemic and meso diastereomers may be smoothly converted to a synthetically useful intermediate with exceptional enantiomeric excess. The stereochemical information generated by means of this catalytic transformation facilitates the easy and rapid completion of the total synthesis of this marine natural product.

α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursors: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center.

This manuscript describes an enantioselective synthesis of the naturally occurring alkaloid citrinadin B. The synthetic effort revealed an anomaly in the original structural assignment that has led to the proposal of a stereochemical revision. This revision is consistent with the structures previously reported for a closely related family of alkaloids, PF1270A-C. The synthesis is convergent and employs a stereoselective intermolecular nitrone cyloaddition reaction as a key step.

An overview of synthetic efforts toward cyathane diterpenoid natural products from the year 2000 to present is provided. The emphasis of this review is the various ring-constructing and stereoforming strategies employed in these synthetic routes. 1 Introduction 2 Overview of the cyathane diterpenoids 2.1 Isolation 2.2 Bioactivity 2.3 Biosynthesis 3 Strategy summary 4 Cyathane core syntheses 4.1 Wender's cyathane core synthesis 4.2 Desma€ ele's cyathane core synthesis 4.3 Takeda's cyathane core synthesis 5Cyathane total syntheses 5.1 Snider's (AE)-allocyathin B 2 and (+)-erinacine A 5.2 Tori's (AE)-allocyathin B 2 5.3 Piers' (AE)-sarcodonin G 5.4 Ward's (AE)-allocyathin B 3 5.5 Ward's (À)-cyathin A 3 5.6 Nakada's (+)-allocyathin B 2 5.7 Nakada's (À)-erinacine B 5.8 Nakada's (À)-erinacine E 5.9 Trost's (+)-allocyathin B 2 5.10 Danishefsky's (À)-scabronine G 5.11 Phillip's (+)-cyanthiwigin U, (+)-cyanthiwigin W, and (À)-cyanthiwigin Z 5.12 Reddy's (+)-cyanthiwigin AC 5.13 Stoltz's (À)-cyanthiwigin F 6 Conclusions 7 Acknowledgements 8 References