Enantioselective Sulfonimidamide Acylation via a Cinchona Alkaloid-Catalyzed Desymmetrization: Scope, Data Science, and Mechanistic Investigation.

Methods to access chiral sulfur(VI) pharmacophores are of interest in medicinal and synthetic chemistry. We report the desymmetrization of unprotected sulfonimidamides via asymmetric acylation with a cinchona-phosphinate catalyst. The desired products are formed in excellent yield and enantioselectivity with no observed bis-acylation.

Exploring Structure-Function Relationships of Aryl Pyrrolidine-Based Hydrogen-Bond Donors in Asymmetric Catalysis Using Data-Driven Techniques.

Hydrogen bond-based organocatalysts rely on networks of attractive noncovalent interactions (NCIs) to impart enantioselectivity. As a specific example, aryl pyrrolidine substituted urea, thiourea, and squaramide organocatalysts function cooperatively through hydrogen bonding and difficult-to-predict NCIs as a function of the reaction partners. To uncover the synergistic effect of the structural components of this catalyst class, we applied data science tools to study various model reactions using a derivatized, aryl pyrrolidine-based, hydrogen-bond donor (HBD) catalyst library.

Catalytic asymmetric C-H insertion reactions of vinyl carbocations.

From the preparation of pharmaceuticals to enzymatic construction of natural products, carbocations are central to molecular synthesis. Although these reactive intermediates are engaged in stereoselective processes in nature, exerting enantiocontrol over carbocations with synthetic catalysts remains challenging. Many resonance-stabilized tricoordinated carbocations, such as iminium and oxocarbenium ions, have been applied in catalytic enantioselective reactions.

Noncovalent Stabilization of Radical Intermediates in the Enantioselective Hydroamination of Alkenes with Sulfonamides.

Noncovalent interactions (NCIs) are critical elements of molecular recognition in a wide variety of chemical contexts. While NCIs have been studied extensively for closed-shell molecules and ions, very little is understood about the structures and properties of NCIs involving free radical intermediates. In this report, we describe a detailed mechanistic study of the enantioselective radical hydroamination of alkenes with sulfonamides and present evidence suggesting that the basis for asymmetric induction in this process arises from attractive NCIs between a neutral sulfonamidyl radical intermediate and a chiral phosphoric acid (CPA).

Linear Regression Model Development for Analysis of Asymmetric Copper-Bisoxazoline Catalysis.

Multivariate linear regression analysis (MLR) is used to unify and correlate different categories of asymmetric Cu-bisoxazoline (BOX) catalysis. The versatility of Cu-BOX complexes has been leveraged for several types of enantioselective transformations including cyclopropanation, Diels-Alder cycloadditions and difunctionalization of alkenes. Statistical tools and extensive molecular featurization has guided the development of an inclusive linear regression model, providing a predictive platform and readily interpretable descriptors.

Cobalt Catalyzed Reductive Spirocyclopropanation Reactions.

Cobalt pyridine-diimine (PDI) complexes catalyze the reductive spirocyclopropanation of terminal 1,3-dienes. -Dichlorocycloalkanes serve as carbene precursors and Zn is used as a terminal electron source. The reaction is effective for a range of -dichloro partners including those containing sulfur and nitrogen heterocycles.

Connecting and Analyzing Enantioselective Bifunctional Hydrogen Bond Donor Catalysis Using Data Science Tools.

The generalization of related asymmetric processes in organocatalyzed reactions is an ongoing challenge due to subtle, noncovalent interactions that drive selectivity. The lack of transferability is often met with a largely empirical approach to optimizing catalyst structure and reaction conditions. This has led to the development of diverse structural catalyst motifs and inspired unique design principles in this field.

Cobalt-Catalyzed Reductive Dimethylcyclopropanation of 1,3-Dienes.

Dimethylcyclopropanes are valuable synthetic targets that are challenging to access in high yield using Zn carbenoid reagents. Herein, we describe a cobalt-catalyzed variant of the Simmons-Smith reaction that enables the efficient dimethylcyclopropanation of 1,3-dienes using a Me CCl /Zn reagent mixture. The reactions proceed with high regioselectivity based on the substitution pattern of the 1,3-diene.

Regioselective Simmons-Smith-type cyclopropanations of polyalkenes enabled by transition metal catalysis.

A [ PDI]CoBr complex (PDI = pyridine-diimine) catalyzes Simmons-Smith-type reductive cyclopropanation reactions using CHBr in combination with Zn. In contrast to its non-catalytic variant, the cobalt-catalyzed cyclopropanation is capable of discriminating between alkenes of similar electronic properties based on their substitution patterns: monosubstituted > 1,1-disubstituted > ()-1,2-disubstituted > ()-1,2-disubstituted > trisubstituted. This property enables synthetically useful yields to be achieved for the monocyclopropanation of polyalkene substrates, including terpene derivatives and conjugated 1,3-dienes.

Dehydrogenative Transformations of Imines Using a Heterogeneous Photocatalyst.

Heterogeneous semiconductors are underexploited as photoredox catalysts in organic synthesis relative to their homogeneous, molecular counterparts. Here, we report the use of metal/TiO particles as catalysts for light-induced dehydrogenative imine transformations. The highly oxophilic nature of the TiO surface promotes the selective binding and dehydrogenation of alcohols in the presence of other oxidizable and Lewis basic functional groups.