Sreekumar Vellalath

Bio: Sreekumar Vellalath is an academic researcher from Council of Scientific and Industrial Research. The author has contributed to research in topics: Carbene & Annulation. The author has an hindex of 12, co-authored 29 publications receiving 1747 citations. Previous affiliations of Sreekumar Vellalath include Max Planck Society & National Institute for Interdisciplinary Science and Technology.

Recent advances in carbon–carbon bond-forming reactions involving homoenolates generated by NHC catalysis

Abstract: Homoenolate, a species containing anionic carbon β to a carbonyl group or a moiety that can be transformed into a carbonyl group, is a potential three carbon synthon. Recent introduction of a protocol for the generation of homoenolate directly from enals by NHC (nucleophilic heterocyclic carbene) catalysis has made it possible to explore the synthetic utility of this unique reactive intermediate. The versatility of NHC-bound homoenolate is illustrated by its annulation with various carbonyl compounds leading to γ-butyrolactones, spiro-γ-butyrolactones, and δ-lactones. Interception of homoenolate with imines afforded γ-lactams and bicyclic β-lactams. Formation of cyclopentenes and spirocyclopentanones respectively by reaction with enones and dienones is also noteworthy. This tutorial review focuses on these and other types of reactions which attest to the synthetic potential of NHC-bound homoenolates in organic synthesis.

N-heterocyclic carbene-catalyzed reaction of chalcones and enals via homoenolate: an efficient synthesis of 1,3,4-trisubstituted cyclopentenes.

Abstract: Nucleophilic heterocyclic carbene-catalyzed cyclopentannulation of enals and chalcones via homoenolate has been observed for the first time. Serendipitously, the reaction lead to a very efficient synthesis of 3,4-trans-disubstituted-1-aryl cyclopentenes instead of the expected cyclopentanones. The strategy works well with thienylidene tetralone also, leading to the tricyclic cyclopentene derivative.

Direct catalytic asymmetric synthesis of cyclic aminals from aldehydes.

Abstract: A highly enantioselective Bronsted acid catalyzed direct synthesis of cyclic aminals from aldehydes has been developed. The methodology has been applied to the first asymmetric synthesis of several antihypertensive aminal drugs including (R)-Thiabutazide.

The Catalytic Asymmetric Acetalization

Abstract: asymmetric Brønsted acid catalysis has recently enabled the enantioselective generation of chiral N,N-, N,O-, and N,Sacetals, either from imines or directly from aldehydes. 3] The success of these reactions is based on the well-established ability of chiral phosphoric acids to direct the enantioselective addition of nucleophiles to imines. However, the corresponding enantioselective additions to oxocarbenium ion intermediates, which are required for obtaining O,O-acetals, are much less developed. Although acetals are among the most common stereocenters in organic molecules, there are only few examples of their catalytic asymmetric synthesis. We have recently reported that chiral Brønsted acids catalyze intramolecular asymmetric transacetalizations and spiroacetalizations generating chiral acetals with high enantioselectivity. 9] However, although our laboratory has pursued the direct asymmetric acetalization of aldehydes with alcohols for many years now, and has investigated numerous chiral Brønsted acid catalysts, unfortunately, very little success towards this goal has been encountered. Here we report that a new member of our recently developed class of chiral confined Brønsted acids finally enables this elusive transformation with excellent selectivity and scope. The summary of our investigations towards asymmetric acetalization with diol 1a and aldehyde 2 a is given in Table 1. A catalytic amount of TRIP (4 a ; Scheme 1), one of the most successful phosphoric acid catalysts, catalyzes the reaction at room temperature giving cyclic acetal 3a with an e.r. (enantiomeric ratio) of 66.5:33.5 and 66 % conversion after 7 days (Table 1, entry 1). The recently developed spirocyclic analogue STRIP (5), which proved to be superior to TRIP on several occasions, gave a slightly improved e.r. of 79:21, but displayed lower reactivity (Table 1, entry 2). Catalysts 4b and 6, which provided excellent results for the related N,Nand N,O-acetalizations of aldehydes, did not give any improvement (Table 1, entries 3 and 4). This striking failure of some of the most successful phosphoric acid catalysts illustrates the general difficulty of dealing with oxocarbenium ion intermediates in Brønsted acid catalysis. Recently, our group has developed a new generation of stronger Brønsted acids, based on a C2-symmetric imidodiTable 1: Catalyst discovery.

Organocatalysis by N-Heterocyclic Carbenes

Abstract: In the investigation of efficient chemical transformations, the carbon-carbon bond-forming reactions play an outstanding role. In this context, organocatalytic processes have achieved considerable attention. 1 Beside their facile reaction course, selectivity, and environmental friendliness, new synthetic strategies are made possible. Particularly, the inversion of the classical reactivity (Umpolung) opens up new synthetic pathways. 2 In nature, the coenzyme thiamine (vitamin B1), a natural thiazolium salt, utilizes a catalytic variant of this concept in biochemical processes as nucleophilic acylations. 3 The catalytically active species is a nucleophilic carbene. 4

N‐Heterocyclic Carbenes as Organocatalysts

Abstract: Organocatalyzed reactions represent an attractive alternative to metal-catalyzed processes notably because of their lower cost and benign environmental impact in comparison to organometallic catalysis. In this context, N-heterocyclic carbenes (NHCs) have been studied for their ability to promote primarily the benzoin condensation. Lately, dramatic progress in understanding their intrinsic properties and in their synthesis have made them available to organic chemists. This has resulted in a tremendous increase of their scope and in a true explosion of the number of papers reporting NHC-catalyzed reactions. Here, we highlight the ever-increasing number of reactions that can be promoted by N-heterocyclic carbenes.