Cobalt‐Catalyzed Asymmetric 1,4‐Reduction of β,β‐Dialkyl α,β‐Unsaturated Esters with PMHS

Abstract

A cobalt‐catalyzed asymmetric reduction of β,β‐dialkyl α,β‐unsaturated esters with polymethylhydrosiloxane (PMHS) was reported to deliver the corresponding esters containing a chiral trialkyl carbon center at β‐position with up to 97 % yield and 98 % ee. The chiral tridentate ligand oxazoline iminopyridine (OIP) could perform well for the asymmetric reduction instead of chiral bidentate ligands. This operationally simple protocol shows a broad scope of substrates using one equivalent of readily available PMHS as a cheap and easy‐to‐handle reductive reagent.

Catalytic Asymmetric Conjugate Reduction

“…In this context, the oxazoline iminopyridine (OIP) ligands developed by Huang [97] and Lu [98–100] found application in ACRs. In 2021, Lu and co‐workers showed that the Co−H complex of L24 is effective in the enantioselective reduction of enoates [101] . Notably, PMHS could be used as a convenient hydride source, and a variety of β,β‐dialkyl enoates 52 were reduced in 86–97 % yield with 74–98 % ee (Figure 19).…”

“…In 2021, Lu and co-workers showed that the CoÀ H complex of L24 is effective in the enantioselective reduction of enoates. [101] Notably, PMHS could be used as a convenient hydride source, and a variety of β,β-dialkyl enoates 52 were reduced in 86-97 % yield with 74-98 % ee (Figure 19).…”

Co(Salox)‐Catalyzed Enantioselective Reduction of α,β‐Unsaturated Esters

“…However, β,β‐dialkyl enoates proved more challenging, with product 3 m giving 94 % yield but only 87 : 13 er or substrate 2 p providing 3 p after in situ lactonization in quantitative yield but racemic fashion. In this regard, this catalytic system shows some complementarity to others for which β,β‐dialkyl substrates perform better than cinnamate derivatives [26,30,37] …”

“…In this regard, this catalytic system shows some complementarity to others for which β,β-dialkyl substrates perform better than cinnamate derivatives. [26,30,37] Finally, the suitability of other EWGs was briefly explored. Nitrile 3 n was obtained in low enantioselectivity (77 : 23 er) albeit in quantitative yield, demonstrating that even weaker activating groups might be at reach with this catalytic system.…”

“…[26][27][28][29] Since this original report by Pfaltz and coworkers in 1989, several progresses have been made, with both anionic or electron donating neutral ligands being employed by Yamada, [30][31][32] Reiser, [33] Kitamura, [34][35] Nishiyama, [36] and Lu (Figure 1). [37][38] Even though each one of these catalytic systems is efficient and has its own merits, the ligands employed often require multistep procedures for their preparation.…”