Sukalyan Bhadra

Design of a New Bimetallic Catalyst for Asymmetric Epoxidation and Sulfoxidation

A new chiral tethered 8-quinolinol-based ligand class is developed. The binuclear titanium complex of the ligand operates through a novel mechanism allowing for the regio- and stereoselective epoxidation of primary and tertiary homoallylic alcohols (up to 98% ee), as well as first examples of 2-allylic phenols (up to 92% ee). The new catalyst system also promotes the asymmetric oxidation of γ-hydroxypropyl sulfides giving an important class of chiral sulfoxides that have been inaccessible to date (up to 95% ee).

Substrate Directed Asymmetric Reactions

Historically, reagent controlled reactions (mechanism controlled reactions) have played a significant role in the asymmetric synthesis of complex structures. In contrast, todays asymmetric synthesis is greatly dependent on substrate directed approaches. In this approach, a polar functional group, namely, a directing group, in the vicinity of the reactive site inside the substrate has been documented to preassociate with the chiral catalyst, which exerts stereodirecting influence by directing the reacting partner toward one of the enantiotopic faces of the reaction center. Those reactions usually proceed through exceptionally ordered transition states and result in extraordinary levels of stereoselection. Within the last four decades, the substrate directed approach has become an indispensible tool for the preparation of complex chiral frameworks starting directly from relatively simple achiral substrate molecules via asymmetric induction or various resolution techniques or both. Likewise, the substrate directed approach has been applied to functionalize enantiopure substrates bearing pre-exisiting stereocenters into complex structures as a single diastereomer. A classical example is Sharpless asymmetric epoxidation of allylic alcohols in which the free hydroxy function acts as an active anchor to a dimeric Ti-catalyst that controls the stereochemical outcome of the epoxidation process by transferring the oxidant enantioselectively. The principal aim of the present review is to give a general overview of substrate directed asymmetric transformations, a topic that has not yet been documented in the form of a concise review of recently developed approaches. Due to the large number of related applications, only recent advances that have been documented within the last two decades have been reviewed. Furthermore, in the current review, we have mainly highlighted asymmetric reactions that are controlled by abundant and frequently used directing groups such as hydroxy, amide, and sulfonamide groups. In addition, selected examples of a few important substrate-directed chemo-, regio-, and diastereoselective reactions have also been included in this review.

Catalytic Asymmetric Synthesis of N‐Chiral Amine Oxides

Direct asymmetric synthesis of N-chiral amine oxides was accomplished (up to 91:9 e.r.) by means of a bimetallic titanium catalyst. A hydroxy group situated at the γ-position of the Nu2005stereocenter enables the desired N-oxidation through dynamic kinetic resolution of the trivalent amine substrates. The method was further extended to the kinetic resolution of racemic γ-amino alcohols with a preexisting stereocenter, giving an important class of enantioenriched (up to 99.9:0.1 e.r.) building blocks that are otherwise difficult to synthesize.

Intramolecular Asymmetric Desymmetrization via Copper Catalysis

Significance: Hydroxyand amino-functionalized C3-fragments play a pivotal role as synthetic intermediates. Whereas enantioselective desymmetrization of diols and glycerol were developed to provide hydroxyl-containing C3-fragments, the corresponding preparation of amino-containing C3-fragments has been rarely documented. Herein, Gu and co-workers present the asymmetric desymmetrization of 1,3-diazido-2-propanols catalyzed by copper–PhBox. Comment: The title transformation is enabled in an enantioselective fashion by CuPF6(MeCN)4 in the presence of (S,S)-PhBox and NaBARF with the larger and non-coordinating BARF– anion. The new method provides reliable access to enantioenriched azido-substituted 5,6-dihydro-1,4-oxazin-2-ones, which can be further converted into useful N-containing scaffolds. CuPF6(MeCN)4 (5 mol%) ligand (6 mol%), NaBARF (6 mol%)

Enantioselective Alkylation of β-Keto Esters

Significance: The Cu(OTf)2/tert-butyl-bis-oxazoline catalyst system allows the asymmetric alkylation of β-keto esters with free benzylic alcohols, for example, xanthydrols as alkylating agents. The reaction is environmentally benign as it generates only water as by-product. Comment: The reaction between the asymmetric Cu(II)-β-keto ester derivative and the in situ generated carbocation proceeds via an SN1 mechanism. Albeit unknown, the water produced has a specific role to facilitate the reaction. X OH