Zinc(II)-Catalyzed Asymmetric Diels–Alder Reaction of (E)-1-Phenyl Dienes with β,γ-Unsaturated α-Ketoesters

Abstract

A highly regio-, diastereo-, and enantioselective Diels−Alder reaction of β,γ-unsaturated α-ketoesters with (E)-1phenyl dienes has been accomplished by using a stable and easily available chiral N,N′-dioxide/zinc(II) complex as catalyst. Only one isomer of the corresponding cyclohexenes with three chiral centers was obtained in good to excellent yields with excellent ee values under mild reaction conditions. The configurations of the product and chiral N,N′-dioxide/zinc(II) catalyst were identified by X-ray diffraction analysis. In addition, a possible catalytic model was proposed to explain the origin of the asymmetric induction.

Theoretical Study on Asymmetric [2 + 2] Cycloaddition of an Alkynone with a Cyclic Enol Silyl Ether Catalyzed by a Chiral N,N′-Dioxide-Zn(II) Complex

“…The mechanism of cycloaddition between an alkynone (R1) and a cyclic enol silyl ether (R2) mediated by a chiral N,N ′-dioxide-Zn­(II) complex (CAT) was further studied at the same theoretical level. On the basis of the X-ray crystal structure of the N,N ′-dioxide-Zn­(II) , complex and our previous works, − a hexacoordinate Zn­(II) complex was considered to be an active species. We first focused on the Zn­(II) complex containing a chiral N,N ′-dioxide ligand L2 with two CH 2 groups in the linkage (see Scheme , m = 1), which was reported in experiments .…”

“…An l -ramipril-derived ligand with two −CH 2 units in the linkage exhibited the best asymmetric induction. In comparison to other chiral N,N ′-dioxide-metal salt catalysts, reports on Zn­(II)-catalyzed asymmetric reaction have been limited. ,, Furthermore, the reaction mechanism of asymmetric [2 + 2] cycloaddition of an alkynone mediated by N,N ′-dioxide/Zn­(NTf 2 ) 2 is still unclear. Herein, we adopted the DFT method to study the reaction mechanism of cycloaddition between an alkynone (R1) and a 1-indanone-derived cyclic enol silyl ether (R2).…”

Further developments of β,γ-unsaturated α-ketoesters as versatile synthons in asymmetric catalysis

“…It is noteworthy that the steric hindrance of amide substituents on the ligand L15 was crucial for enantiocontrol. Subsequently, a catalytic asymmetric Diels-Alder reaction of β,γ -unsaturated α -ketoesters with ( E )-1phenyl dienes 70 was accomplished by the same group in 2018, using a chiral N , N ′-dioxide/zinc(II) complex as catalyst ( Scheme 10 B) ( Xiong et al., 2018 ). Excellent diastereo- and enantioselectivities (88–99% ee, >19:1 dr) were observed.…”

Recent developments in enantioselective zinc-catalyzed transformations

“…Indeed, the chiral zinc catalyst in situ generated from 10 mol% of this ligand and the same quantity of Zn(OTf) 2 in dichloromethane as solvent was found to promote this reaction at 35 °C, resulting in the formation of the corresponding chiral functionalized spirooxindoles 8 exhibiting three contiguous stereocenters in moderate yields (51-68%) albeit as almost single diastereo-(>90% de) and enantiomers (98À>99% ee) regardless Scheme 3. Diels-Alder cycloaddition of (E) 1-phenyl dienes with b,c-unsaturated a ketoesters in the presence of a N,N 0 -dioxide ligand [19].…”

“…Another chiral N,N 0 -dioxide ligand was later employed by these authors to promote highly regio-, diastereo-, and enantioselective Diels-Alder cycloaddition of (E) 1-phenyl dienes 9 with b,cunsaturated a ketoesters 10 [19]. Only one diastereomer (>90% de) of the corresponding cyclohexenes 11 containing three contiguous stereocenters was obtained in all reactions when catalyzed at 35 °C by a combination of 5 mol% of ligand 12 and 5 mol% of Zn (OTf) 2 in DCE as solvent (Scheme 3).…”