Electron-Deficient Alkynes as Dipolarophile in Pd-Catalyzed Enantioselective (3 + 2) Cycloaddition Reaction with Vinyl Cyclopropanes

Abstract

The activated alkynes have been used successfully for the first time as the dipolarophile in the palladium-catalyzed asymmetric (3 + 2) cycloaddition, affording highly functionalized cyclopentenes in good to high yields with high chemoselectivities and good to high enantioselectivities. The introduction of an additional carbonyl group at the α-position of the alkynyl esters is the key to activating the carbon–carbon triple bond. The reaction process was investigated, and an inverse process of Pd-catalyzed (3 + 2) cycloaddition was observed.

Development of Dipolarophiles for Catalytic Asymmetric Cycloadditions through Pd‐π‐Allyl Zwitterions

“…The issue of chemoselectivity was solved by performing the reaction using ( R )‐SEGPHOS ( L9 ) as ligand in a mixed solvent of DCM and DME (1.2/0.8) at 10 °C (Table 8). [42] The cycloaddition is applicable to varieties of methyl 2‐oxobut‐3‐ynoates 37 with different substituents at different position of phenyl ring as well as heteroaryl and naphthyl groups, delivering the corresponding cycloadducts in high yield with high chemo‐ and enantioselectivity. Alkyl and Et 3 Si substituted alkynyl α‐ketoesters were competent reactants.…”

“…Three alkynes such as methyl 3‐phenylpropiolate, 4‐( p ‐tolyl)but‐3‐yn‐2‐one, and dimethyl but‐2‐ynedioate were treated with vinyl cyclopropane 36 in the presence of Pd(OAc) 2 and ( rac )‐BINAP [42] . However, the cycloadditions didn't take place probably due to their low reactivity (eq 1, Scheme 15).…”

Asymmetric Catalytic Reactions of Donor–Acceptor Cyclopropanes

“…successfully synthesized chiral cyclopentenes by using ketoester‐ or 1,2‐dione‐activated alkynes (Scheme 22 b). [37a] The use of isatin dipolarophiles allowed for the synthesis of enantioenriched tetrahydrofuran derivatives. In this reaction, the diastereoselectivity was improved by the addition of LiCl (Scheme 22 c).…”

Cyclopentene Assembly by Microwave-Assisted Domino Reaction of Donor–Acceptor Cyclopropanes with Ketals

“…16 Transitionmetal-catalyzed [3+2]-cycloaddition can be employed for a broad spectrum of alkynes including electron-deficient ones (Scheme 1a). 17 However, only alkenyl-substituted DA cyclopropanes participate in this reaction. The related radical-induced cycloadditions have similar restrictions on the structure of the alkynes and DA cyclopropanes, and they produce cyclopentenes in low-to-moderate yields only.…”