Amino Acid Derived Phosphine‐Catalyzed Enantioselective 1,4‐Dipolar Spiroannulation of Cyclobutenones and Isatylidenemalononitrile

Abstract

Cyclobutenones have been explored as a new type of chiral 1,4-dipole four-carbon synthon, which readily undergoes organophosphine-mediated C-C bond cleavage and asymmetric intermolecular 1,4-dipolar spiroannulation with isatylidenemalononitrile in the presence of amino acid-derived chiral phosphine catalyst to furnish enantioenriched 3-spirocyclohexenone 2-oxindoles in good yield with up to 87% ee. To our knowledge, this is the first example of asymmetric transformation of cyclobutenones and the phosphine-catalyzed asymmetric 1,4-dipolar cycloaddition consisting of C-C bond activation is unprecedented.

Molecular diversity of spirooxindoles. Synthesis and biological activity

“…A simple bisthiourea 321 was used as the organocatalyst, that provided the products in excellent yields and stereoselectivity (>99:1 dr, up to 99 % ee) [184].…”

Enantioselective Construction of All‐Carbon Quaternary Stereogenic Centers by Using Phosphine Catalysis

“…Recently, Zhang and co‐workers reported a unique utilization of cyclobutenenone as a C4 synthon in an asymmetric [4+2] annulation reaction . By using amino‐acid‐derived phosphine P20 , an enantioselective [4+2] annulation between cyclobutenones 101 and isatin‐derived alkenes 102 proceeded readily to afford spirocyclohexane oxindoles 103 in excellent chemical yields and high enantioselectivities.…”

Cyclobutenones and Benzocyclobutenones: Versatile Synthons in Organic Synthesis

“…Inspired by the phosphine-catalyzed ringo peningr eaction, in 2015 Zhang and co-workers reported the enantioselective synthesis of spirocycles 108 through af ormal [4+ +2] cycloaddition between cyclobutenones 106 and isatylidenemalononitriles 107,c atalyzedb ya mino acid-derived chiral phosphines 109 (Scheme 35). [44] Comparedw ith phosphine catalysts bearing as ingleo rw eak double H-bond donor( e.g., 109 a-e), phenylalanine-derived catalyst 109 f,w ith as trong double H-bond donor moiety,p rovedo ptimal, affording the cycloadduct in excellent yield and good enantioselectivity.N aI was proposed to provide ac ounterion that stabilized the zwitterionic intermediate. The substitution pattern of cyclobutenones only had amarginal effect on reactivity and enantioselectivity.…”