Asymmetric Synthesis of a Fused Tricyclic Hydronaphthofuran Scaffold by Desymmetric [2+2+2] Cycloaddition

Abstract

A rhodium(I)‐BINAP‐catalyzed highly enantioselective [2+2+2] cycloaddition of enynes with alkynes has been developed. Diverse fused tricyclic hydronaphthofuran scaffolds with three consecutive stereogenic centers were constructed in one step from easily available materials with excellent chemo‐, regio‐, diastereo‐, and enantioselectivity. Notable features of these reactions include 100 % atom economy, very broad scope, and mild reaction conditions.

Mechanism and origin of regioselectivity in Rh-catalyzed desymmetric [2 + 2 + 2] cycloaddition: charge versus π–π stacking interaction

“…Recently, the Xu group reported a straightforward method to synthesize fused tricyclic hydronaphthofuran derivatives by rhodium-catalyzed desymmetric [2 + 2 + 2] cycloadditions of cyclohexadienone alkynes with terminal alkynes (Scheme 2). 6 The broad substrate scope, mild reaction conditions and excellent enantio-and regioselectivity make this reaction an efficient method for the synthesis of fused tricyclic hydronaphthofuran derivatives. Interestingly, the choice of substituents on the phenyl groups of the terminal alkynes exerts a great influence on the regioselectivity of terminal alkyne insertion to form different regioisomeric products.…”

Dual C(sp3)–H Functionalization of Cyclic Ethers via Singlet Oxygen-Mediated Ring Opening and Ring Closing

“…A s the structural core in numerous biologically important natural products and synthetic compounds, hydrobenzofurans/pyrans/dioxins are considered attractive targets for synthetic chemists. 1 Although many catalytic systems employing transition-metal-catalyzed reactions 2 (Pd, 3 Cu, 4 Ni, 5 or Rh 6 ) have been developed for the synthesis of such structures, metal-free and photocatalytic direct hydrofuran/ pyran/dioxin synthesis from easily available and inexpensive cyclic ethers in this area has been challenging.…”

Asymmetric synthesis of tricyclic 6,5,5-fused polycycles by the desymmetric Pauson–Khand reaction

“…9,10 In 2020, we reported the first rhodium-BINAPcatalyzed desymmetric [2 + 2 + 2] reaction of 1 with alkynes generating fused tricyclic hydronaphthofuran scaffolds with three consecutive stereogenic centers in a single step. 11 This reaction proceeded with a desymmetric oxidative cyclization of enynes 1 with a chiral Rh(I) catalyst, generating the key chiral cyclic rhodium intermediate M, followed by alkyne insertion. In this context, we investigated if CO coordination and insertion could produce chiral 6,5,5-fused polycycles, namely the asymmetric PK reaction, when this reaction was performed under a CO atmosphere.…”