A Highly Diastereo‐ and Enantioselective Reaction for Constructing Functionalized Cyclohexanes: Six Contiguous Stereocenters in One Step

Abstract

Sechs auf einen Streich: Sechs benachbarte Stereozentren, darunter ein quartäres, sowie drei C‐C‐Bindungen werden durch eine neue kupferkatalysierte Tandemreaktion eingeführt, wobei starre chirale Diaminliganden für hervorragende Stereoselektivitäten sorgen (vollständige Diastereoselektivität und hohe Enantioselektivität). Unter milden Reaktionsbedingungen werden die Produkte in hohen Ausbeuten erhalten (siehe Schema).

Green Copper Catalysis in Enantioselective Domino Reactions

“…Performed in the presence of a chiral catalyst in situ generated from CuCl and the same chiral phosphite ligand 68, the domino double Michael reaction afforded the corresponding chiral products 73 bearing three contiguous stereocenters in moderate to good yields (55-87%), and both remarkable diastereo-and enantioselectivities (>90->98% de and 94-97% ee, respectively), as depicted in Scheme 22. In 2012, enantioselective copper-catalyzed pseudo-three-component domino Michael/Henry reactions were also described by these authors [30]. They involved α-ketoesters 74 and two equivalents of nitroalkenes 72' as substrates, which led, in the presence of a chiral copper catalyst in situ generated from Cu(OAc) 2 (H 2 O) and chiral 1,2-diamine ligand 75, to the corresponding highly functionalized cyclohexanes 76 bearing six stereogenic centers in moderate to excellent yields (42-95%), almost complete diastereoselectivity (>90% de) and moderate to excellent enantioselectivities (60-98% ee), as shown in Scheme 23.…”

The crystal structure of 4-(4-chlorophenyl)cyclohexane-1-carboxylic acid, C13H15ClO2

“…Especially, these asymmetrically substituted products, are usually synthesized by the Michael addition [11][12][13][14][15]. However, the corresponding acids are rare [16].…”

Recent Developments in Enantioselective Metal‐Catalyzed Domino Reactions

“…In 2012, Huang et al. reported a novel highly enantio‐ and diastereoselective copper‐catalyzed domino Michael/Michael/Henry reaction 142. This remarkable pseudo‐three‐component reaction involved two equivalents of nitroalkenes 10a–l and α‐keto esters 321a–k , which afforded the corresponding highly functionalized cyclohexanecarboxylates 322a–u bearing six stereogenic centers including one quaternary one, in excellent yields, diastereo‐, and enantioselectivities of up to >90% de , and 98% ee , respectively (Scheme ).…”