Cooperative copper-squaramide catalysis for the enantioselective N–H insertion reaction with sulfoxonium ylides

Abstract

The first examples of a highly efficient and enantioselective carbene-mediated insertion reaction, from a sulfur ylide, are described.

Organocatalytic asymmetric synthesis of α-amino esters from sulfoxonium ylides

“…5 Unfortunately, it resulted in completely no reactivity. Furthermore, squaramide B alone was also catalytically incompetent although it could serve as a cocatalyst for the Cu-catalyzed N−H insertion (entry 2), 6 which corroborated the essential role of a metal catalyst as well as the carbene intermediate. We next resorted to the stronger Brønsted acids, chiral phosphoric acids (CPAs), 9 in hope of achieving sufficient reactivity.…”

“… 5 During the preparation of this manuscript, Burtoloso and coworkers reported the use of a copper/squaramide co-catalyzed system to achieve the asymmetric N–H insertion of α-carbonyl sulfoxonium ylides, leading to various α-amino esters with moderate enantioselectivities (up to 84% ee). 6 Mechanistically, this reaction shares the same copper carbene intermediate as those from diazo esters, i.e. , the copper catalyst is essential for the observed reactivity ( Scheme 1 ).…”

“…Recently, the laboratories of Burtoloso and us have demonstrated that sulfoxonium and sulfonium ylides can be activated by chiral Brønsted acids either by weak hydrogen bonding or strong protonation to form σ bonds, respectively, for asymmetric induction in the following bond-forming events. 6,7 b We wondered whether such interactions could be utilized for the successful amination of sulfoxonium ylides, which are much more stable and practically useful than their analogues, sulfonium ylides. However, sulfoxonium ylides are less basic due to the polarized S O bond.…”

Asymmetric transformations from sulfoxonium ylides

“…Although the metal-carbene mediated X–H insertion reaction from sulfoxonium ylides has been known since 1993, it was only in 2021 that the first highly enantioselective carbene mediated transformation using sulfoxonium ylide was published, by Burtoloso's group ( Scheme 15B ). 139 Using a copper-bifunctional-squaramide cooperative catalytic system, the authors synthesized 37 α-arylglycine esters (112) in 49–96% yields and 40–84% ee values (90–98% ee after one recrystallization). In contrast to the previously reported novel enantioselective insertion methodology, which requires long reaction periods and prolonged cooling, this methodology works best at 60 °C, and the reaction reaches completion within 1 h. In addition, it utilizes the inexpensive copper metal and does not require special conditions (benchtop procedure).…”

“…This strategy allows straightforward access to a variety of bioactive compounds. 139 In 2020, Sun and co-workers developed a protocol for asymmetric N–H insertion, using a combination of prochiral α-carbonyl sulfonium ylide and arylamines. 57 As discussed previously, sulfonium ylides present some disadvantages when compared to the sulfoxonium ylides, but nonetheless were suitable substrates for this chiral phosphoric acid promoted reaction.…”