Temperature‐Dependent Cinchona Alkaloid Squaramide‐Catalyzed Asymmetric Formal [3+2] Cycloaddition of Isocyanoacetates with β‐Trifluoromethylated Enones

Abstract

An efficient temperature‐dependent organocatalyzed asymmetric formal [3+2] cycloaddition reaction of α‐substituted isocyanoacetates to β‐trifluoromethylated enones by cinchona alkaloid‐derived squaramide has been investigated, affording the optically active trifluoromethylated 2‐pyrrolines in excellent yields (up to 98 %) and high stereoselectivities (>20:1 dr, up to >99 % ee) under mild conditions.

Catalytic Enantioselective Isocyanide‐Based Reactions: Beyond Passerini and Ugi Multicomponent Reactions

“…Concurrently, a variant of the same reaction was also reported by Zhao et al. by employing a dihydroquinine‐derived squaramide catalyst [52] . Following these achievements, a series of reports involving electron‐deficient terminal olefins including vinyl ketones, [53a] α‐tosyloxyacrylates, [53b] α‐thioacrylates and α‐phthalimidoacrylates [53c] were independently published by the groups of Escolano and Shao.…”

Squaramide Catalyzed Asymmetric Synthesis of Five‐ and Six‐Membered Rings

“…It is interesting to note that F was the optimal catalyst along with lewis acid cocatalyst for the reaction with methyl and tert ‐butyl isocyanoacetates delivering trans diastereomer as the major one whereas cis isomer was obtained as major from methyl 2‐isocyano‐2‐phenylacetate in the presence of Q′ /Ag + catalytic system (Scheme 87b). In this context, another report was published involving squaramide catalyzed formal (3+2) annulation between α ‐ substituted isocyanoacetate and β ‐trifluoromethyl enone leading to the access of chiral 2,3‐dihydro‐1H‐pyrrole derivatives bearing a trifluoromethylated tertiary and a quaternary stereocenters (not shown in the scheme) [135] …”

“…In this context, another report was published involving squaramide catalyzed formal (3 + 2) annulation between αsubstituted isocyanoacetate and βtrifluoromethyl enone leading to the access of chiral 2,3dihydro-1H-pyrrole derivatives bearing a trifluoromethylated tertiary and a quaternary stereocenters (not shown in the scheme). [135] Chiral squaramide has been merged with gold (I) catalyst to accomplish a three component two step method. The reaction is initiated by stereoselective 1,2-addition of propargyl alcohol 328 to pyrazolinone derived ketimine 329 under the control of squaramide M catalysis delivering 330 as the intermediate product in 5 minutes.…”

β‐Trifluoromethyl α,β‐unsaturated Ketones: Efficient Building Blocks for Diverse Trifluoromethylated Molecules

“…Here also the organocatalyst 179 was cinchona alkaloid-base squaramide compound, however the important criterion for the [3 + 2] cyclization process is the temperature, which reduces the usage of acid-based cyclization step. [97] Scheme 46. The synthesis of pyrroline derivatives using β-CF 3 enones.…”

“…In continuation of their work, recently Zhao and coworkers reported an efficient temperature‐dependent organocatalysed asymmetric [3+2] cycloaddition reaction between α ‐substituted isocyanoacetates 177 and β ‐trifluoromethyl enones 3 which is in contrast to their previous report which involves two step reaction (Scheme 48). Here also the organocatalyst 179 was cinchona alkaloid‐base squaramide compound, however the important criterion for the [3+2] cyclization process is the temperature, which reduces the usage of acid‐based cyclization step [97] …”