Diastereoselective 1,6-Addition of α-Phosphonyloxy Enolates to para-Quinone Methides

Abstract

The addition of α-ketoamide to p-quinone methide initiated by dialkylphosphite in the presence of organic base 1,8diazabicyclo(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.

[1,2]‐Phospha‐Brook Rearrangement as Tool for Generation of Anionic Nucleophiles in Addition Reactions under Brønsted Base Catalysis

“…Later, the electrophiles for the trapping of enolate E derived from isatin derivatives were expanded, and the diastereoselective reactions with β‐nitrostyrenes 23 [17] and para ‐quinone methides 26 [18] were reported (Scheme 11). Both reactions proceeded in a highly chemoselective manner to provide the corresponding adducts in high yields.…”

Stereoselective Reductive Coupling Reactions Utilizing [1,2]-Phospha-Brook Rearrangement: A Powerful Umpolung Approach

“…35 In this context, our group exploited these reactive synthons for synthesizing highly diastereoselective phosphate bearing 1,6-adducts 78, utilizing Brønsted base-catalyzed [1,2]phospha-Brook rearrangement/addition reactions (Scheme 18). 36 These adducts could further be efficiently transformed The above transformation involves 1,6-addition of isatins to p-QMs via [1,2]-phospha-Brook rearrangement, which further paved the way to the development of a fascinating Lewis-acidmediated one-pot, two-step homologation approach installing p-QM-embedded 2-quinolinone cores 81 in highly regioselective fashion (Scheme 19). 37 The domino reaction proceeds through regioselective opening of cyclopropane ring 85 formed through P(NMe 2 ) 3 -mediated [1,2]-phospha-Brook rearrangement of isatins 20 and p-QMs 77, followed by ring expansion of 86 through neighboring group participation.…”

Ring Expansion of Isatins via 1,2-Phospha-Brook Rearrangement: A Route to the Synthesis of 2-Quinolinone-Derived p-Quinone Methides

“…The organic layer was separated, and the aqueous layer was washed with DCM (3 mL × 5 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. 21 To an oven-dried 5 mL round-bottom flask charged with a magnetic bar was added compound 3a (85 mg, 0.2 mmol) and dissolved in toluene (2 mL) at −10 °C, followed by AlCl 3 (133 mg, 5 equiv) in an argon environment and allowed to react at the same temperature. The reaction mixture was monitored by TLC.…”

“…3-(3-(tert-Butyl)-4-hydroxyphenyl)-4-phenylquinolin-2(1H)-one (5e). 21 To an oven-dried 5 mL round-bottom flask charged with a magnetic bar was added compound 3a (85 mg, 0.2 mmol) and dissolved in toluene (2 mL) at −10 °C, followed by AlCl 3 (133 mg, 5 equiv) in an argon environment and allowed to react at the same temperature. The reaction mixture was monitored by TLC.…”