The sorbicillinoids are a family of hexaketide metabolites that have been isolated from a variety of fungal sources, collected from both marine and terrestrial sources. Since 1948, the family has grown in size to include over 50 members, many of which have complex, highly oxygenated, bicyclic and tricyclic frameworks. In conjunction with their biological activity, the structural complexity of these structures has inspired several synthetic campaigns and has also led to controversy surrounding the biosynthetic pathway responsible for the natural production of these compounds. Through this review, we aim to give a historical perspective to each of these areas and hope to inspire new avenues of research for addressing the knowledge gaps that still exist.

Enantioconvergent catalysis is a powerful synthetic method that converts a racemic stereogenic substrate into an enantiomerically enriched product with a theoretical yield of 100 % in a single operation.[1] Conceptually, a catalytic system for such a reaction must achieve a stereomutation [2] or stereoablation [3,4] of the substrate (or an intermediate), followed by an enantioselective conversion into product (Figure 1, compare pathways I and II). A number of catalytic processes of this type have been developed, including chemical, enzymatic, and chemoenzymatic strategies. [1,2,4] Racemic compounds that contain quaternary carbon centers are typically unsuitable substrates for enantioconvergent catalysis because of the difficulty associated with CÀC bond cleavage in the stereomutative or stereoablative process. [5,6] Herein, we describe the first catalytic system for the deracemization of quaternary carbon stereocenters. Our enantioconvergent method converts racemic a-substituted 2-carboxyallylcyclohexanones into highly enantioenriched cycloalkanones that bear quaternary stereocenters through catalytic asymmetric decarboxylative allylation.We recently reported the first catalytic asymmetric allylation methods for the synthesis of 2-alkyl-2-allylcycloalkanones (Scheme 1).[7] These reactions, based on racemic transformations reported in the early 1980s by Tsuji, [8] use enol carbonates and silyl enol ethers along with various allyl carbonates and a Pd 0 catalyst supported by a chiral phosphinooxazoline ligand (e.g., 1). [9][10][11] To demonstrate the utility of this methodology, we have started to employ these allylations as the key enantioselective reaction in multistep syntheses. In one such project, we required the substituted cyclohexenone 6 (Scheme 2). Unfortunately, the preparation of the allylation precursor 4 (R = CO 2 allyl or SiMe 3 ) was hampered by nonselective enolization of 3 to form inseparable mixtures of 4 and 5, which resulted in significant amounts of 7 after allylation.Prompted by the need for better position control in these synthetic sequences, we sought mechanistically guided alternatives to the reactions depicted in Scheme 1. To this end, we synthesized dideuterated carbonate 8 and trideuterated carbonate 9. When 8 was subjected to our standard conditions for allylation, the deuterium label was almost evenly scrambled between the termini of the allyl fragment in the product (Scheme 3 a).[12] In a separate crossover experiment, the reaction of equimolar amounts of carbonates 8 and 9 was performed under our standard allylation conditions. As expected, NMR spectroscopic analysis of the product showed deuterium scrambling between the allyl termini, but interestingly, mass spectrometric analysis of the product showed an almost perfect statistical distribution of enolate and allyl fragment pairs with four possible masses (Scheme 3 b).[12] Thus, all six possible products were formed in the reaction including those derived from crossover reactions. Although the specific details associated with the en...

Enantioconvergent catalysis is a powerful synthetic method that converts a racemic stereogenic substrate into an enantiomerically enriched product with a theoretical yield of 100 % in a single operation.[1] Conceptually, a catalytic system for such a reaction must achieve a stereomutation [2] or stereoablation [3,4] of the substrate (or an intermediate), followed by an enantioselective conversion into product (Figure 1, compare pathways I and II). A number of catalytic processes of this type have been developed, including chemical, enzymatic, and chemoenzymatic strategies. [1,2,4] Racemic compounds that contain quaternary carbon centers are typically unsuitable substrates for enantioconvergent catalysis because of the difficulty associated with CÀC bond cleavage in the stereomutative or stereoablative process. [5,6] Herein, we describe the first catalytic system for the deracemization of quaternary carbon stereocenters. Our enantioconvergent method converts racemic a-substituted 2-carboxyallylcyclohexanones into highly enantioenriched cycloalkanones that bear quaternary stereocenters through catalytic asymmetric decarboxylative allylation.We recently reported the first catalytic asymmetric allylation methods for the synthesis of 2-alkyl-2-allylcycloalkanones (Scheme 1).[7] These reactions, based on racemic transformations reported in the early 1980s by Tsuji, [8] use enol carbonates and silyl enol ethers along with various allyl carbonates and a Pd 0 catalyst supported by a chiral phosphinooxazoline ligand (e.g., 1). [9][10][11] To demonstrate the utility of this methodology, we have started to employ these allylations as the key enantioselective reaction in multistep syntheses. In one such project, we required the substituted cyclohexenone 6 (Scheme 2). Unfortunately, the preparation of the allylation precursor 4 (R = CO 2 allyl or SiMe 3 ) was hampered by nonselective enolization of 3 to form inseparable mixtures of 4 and 5, which resulted in significant amounts of 7 after allylation.Prompted by the need for better position control in these synthetic sequences, we sought mechanistically guided alternatives to the reactions depicted in Scheme 1. To this end, we synthesized dideuterated carbonate 8 and trideuterated carbonate 9. When 8 was subjected to our standard conditions for allylation, the deuterium label was almost evenly scrambled between the termini of the allyl fragment in the product (Scheme 3 a).[12] In a separate crossover experiment, the reaction of equimolar amounts of carbonates 8 and 9 was performed under our standard allylation conditions. As expected, NMR spectroscopic analysis of the product showed deuterium scrambling between the allyl termini, but interestingly, mass spectrometric analysis of the product showed an almost perfect statistical distribution of enolate and allyl fragment pairs with four possible masses (Scheme 3 b).[12] Thus, all six possible products were formed in the reaction including those derived from crossover reactions. Although the specific details associated with the en...

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.