Organocatalyzed Asymmetric Tandem Intramolecular oxa‐Michael Addition/Electrophilic Thiocyanation: Synthesis of Chiral α‐Thiocyanato Flavanones

Abstract

An efficient bifunctional cinchona alkaloids‐catalyzed asymmetric tandem intramolecular oxa‐Michael addition/electrophilic thiocyanation of alkylidene β‐ketoesters with N‐thiocyanatosuccinimide (NTS) was developed. A series of chiral α‐thiocyanato flavanones containing two vicinal stereocenters including an all‐carbon quaternary center were prepared in good yields with excellent diastereo‐ and enantioselectivities (up to 97% ee) under mild conditions, and a successful scale up preparation of our protocol was also demonstrated.

C‐Centered radical intermediates for C(sp3)‐H bonds functionalization: An emerging approach towards alkyl thiocyanates

“…More recently, the development of electrophilic thiocyanate reagents, [21] mainly represented by imide‐based compounds ( i. e. N ‐thiocyanatosuccinimide (NTS), N ‐thiocyanatophthalimide (NTP)) or the N ‐thiocyanatosaccharin, for example, has also enabled important contributions to direct thiocyanation transformations. In particular, these reagents have been successfully used in the recent design of rare enantioselective thiocyanation reactions (Scheme 1B, 2 electrons strategies) [25–29] …”

Organophotocatalytic Remote Thiocyanation Reaction via Ring‐Opening Functionalization of Cycloalkanols

“…In recent years, electrophilic C−H thiocyanation reactions have been developing rapidly due to its mild reaction conditions, inexpensive non‐toxic reagents, and high efficiency. However, the synthesis of alkyl thiocyanates through electrophilic reactions is currently limited to substitution reactions of β ‐keto esters, [6a] oxoindole, [6b] and bifunctionalization reactions of unsaturated hydrocarbons as well [6c–h] . It is particularly challenging to achieve simple and efficient synthesis of terminal alkyl thiocyanates [7,8] …”

Asymmetric Hydrogenation by Relay Catalysis with FLPs and CPAs: Stereodivergent Synthesis of 3-Substituted Flavanones

“…Very recently, we developed a relay catalysis strategy with achiral boranes and chiral phosphoric acids (CPAs) for the asymmetric hydrogenation of 3-substituted chromones, affording the desired products in ≤95% ee (Scheme b) . Despite these advances, to the best of our knowledge, the asymmetric hydrogenation of 2,3-disubsituted chromones to access flavanones or chromanones containing two contiguous stereogenic centers has rarely been reported and remains a challenge . As a detour, we expect to employ racemic 3-alkylidene flavanones 1 as substrates for the asymmetric hydrogenation via relay catalysis to demonstrate the stereodivergent synthesis of 3-substituted flavanones 2 and 3 in one pot (Scheme c).…”