Catalytic Asymmetric Michael Addition/Cyclization of Isothiocyanato Oxindoles: Highly Efficient and Versatile Approach for the Synthesis of 3,2′‐Pyrrolidinyl Mono‐ and Bi‐spirooxindole Frameworks

Abstract

A‐spiro‐ing to greatness: The catalytic asymmetric Michael addition/cyclization of isothiocyanato oxindoles has been realized. This versatile approach provides an easy and highly efficient way to access not only the enantioselective synthesis of 3,2′‐pyrrolidinyl spirooxindole frameworks, but also the construction of enatiomerically enriched bi‐spirooxindoles containing three contiguous stereocenters and two spiro‐quaternary centers (see scheme).

Catalytic Asymmetric 1,2‐Addition of α‐Isothiocyanato Phosphonates: Synthesis of Chiral β‐Hydroxy‐ or β‐Amino‐Substituted α‐Amino Phosphonic Acid Derivatives

“…Catalytic asymmetric transformations employing α‐isothiocyanato compounds have recently been found to be very useful processes for the enantioselective construction of a variety of useful chiral compounds 12. As part of our ongoing interest in transformations involving α‐isothiocyanato compounds12i,j,n,o,q,r and the asymmetric synthesis of amino phosphonic acid derivatives,13 we focused our attention on the development of a novel synthetic method involving the use of isothiocyanato compounds for the construction of functionalized chiral α‐amino phosphonic acid derivatives. The poor nucleophilicity of anionic α‐amino phosphonic acid equivalents results in a small equilibrium constant for their addition to electrophiles.…”

Organocatalyzed Asymmetric Reaction Using α-Isothiocyanato Compounds

“…Organocatalyzed Asymmetric Reaction Using α-Isothiocyanato Compounds http://dx.doi.org/10.5772/62765 attribute to the stereoselectivity and reactivity of the α-isothiocyanato compounds with electron-deficient olefins is challenging. As shown in Scheme 13, rosin-derived thiourea (7b) catalyzed the asymmetric cascade Michael/cyclization reaction of α-isothiocyanato imides (1b, 4a, and 5) with various methyleneindolinones (35), affording the densely functionalized 3,3′pyrrolidonyl spirooxindoles (36)(37)(38) in excellent results (up to 99% yield, >20:1 dr, and >99% ee).…”

Core‐Structure‐Motivated Design of Iminium–Enolate Organocascade Reactions: Enantioselective Syntheses of 5,6‐Dihydroindolizines

“…[2] The 5,6,7,8-tetra-and 5,6-dihydroindolizine frameworks ( Figure 1) have recently drawn tremendous interest from both synthetic and medicinal chemists because of their properties as anti-tumor, [3a,g] antileukemia, [3b] anti-cholinergic agents, [2a] and other important biological activities. Recently, there has been considerable progress in the field of organocatalytic asymmetric synthesis of other important nitrogen-containing heterocycles based on the (ox)indole skeleton, [6,7] but the enantioselective synthesis of pyrrole derivatives has been less studied because of the difficulties in stereocontrol and mode of activation. [4] Thus, the design of new synthetic methods to provide molecules in this class of compounds is of interest, and intramolecular cyclization of intermediates using metal-catalyzed, [5c-g] radical, [5h-i] and base-induced processes have been reported.…”

“…Recently, there has been considerable progress in the field of organocatalytic asymmetric synthesis of other important nitrogen-containing heterocycles based on the (ox)indole skeleton, [6,7] but the enantioselective synthesis of pyrrole derivatives has been less studied because of the difficulties in stereocontrol and mode of activation. Recently, there has been considerable progress in the field of organocatalytic asymmetric synthesis of other important nitrogen-containing heterocycles based on the (ox)indole skeleton, [6,7] but the enantioselective synthesis of pyrrole derivatives has been less studied because of the difficulties in stereocontrol and mode of activation.…”

“…[5] Current synthetic methods to access these motifs require multi-steps and are largely racemic. Recently, there has been considerable progress in the field of organocatalytic asymmetric synthesis of other important nitrogen-containing heterocycles based on the (ox)indole skeleton, [6,7] but the enantioselective synthesis of pyrrole derivatives has been less studied because of the difficulties in stereocontrol and mode of activation. To date, there have been few or no reports concerning catalytic asymmetric methodologies that systematically address the construction of privileged indolizine core scaffolds of this type.In view of the operational and economical advantages associated with organocatalysis, our laboratory has been engaged in the design of broadly useful new strategies for enantioselective oxindole syntheses using enamine, iminium, hydrogen-bonding, alkaloid, and phosphine catalysis.…”