Diastereoselective 1,6-Addition of α-Phosphonyloxy Enolates to <i>para</i>-Quinone Methides

Abstract

The addition of α-ketoamide to p-quinone methide initiated by dialkylphosphite in the presence of organic base 1,8-diazabicyclo(5.4.0)undec-7-ene (DBU) is explored. Coupling of dialkylphosphites to α-ketoamides in the presence of a base follows [1,2]-phospha-Brook rearrangement, generating corresponding α-phosphonyloxy enolates that are subsequently seized by p-quinone methides (p-QMs). The two-step one-pot 1,6-conjugate addition provides effective access to a series of isatin-incorporated phosphate-bearing 1,6-adducts having two vicinal tertiary carbons with up to 90% yield and >20:1 dr.

Topics & Concepts