Palladium-catalyzed coupling of allenylphosphonates, phenylallenes, and allenyl esters: remarkable salt effect and routes to novel benzofurans and isocoumarins

Abstract

Coupling reactions of allenylphosphonates (OCH₂CMe₂CH₂O)P(O)CH=C=CRR' [R, R' = H (1a), R = H, R' = Me (1b), R = R' = Me (1c)] with aryl iodides, iodophenol, and iodobenzoic acid in the presence of palladium(II) acetate are investigated and compared with those of phenylallenes PhCH=C=CR₂ [R = H (2a), Me (2b)] and allenyl esters EtO₂CCH=C=CR₂ [R = H (2c), Me (2d)]. While 1b and 1c couple with different stereochemical outcomes using PhI in the presence of Pd(OAc)₂/PPh₃/K₂CO₃ to give phenyl-substituted 1,3-butadienes, 1a does not undergo coupling but isomerizes to the acetylene (OCH₂CMe₂CH₂O)P(O)C?CMe (7). In the reaction of 1c with PhI, use of K₂CO₃ affords the butadiene (Z)-(OCH₂CMe₂CH₂O)P(O)CH=C(Ph)-C(Me)=CH₂ (12); in contrast, the use of Ag₂CO₃ leads to the allene (OCH₂CMe₂CH₂O)P(O)C(Ph)=C=CMe₂ (20), showing that these bases differ very significantly in their roles. The reaction of 1a with PhI or PhB(OH)₂ in the presence of Pd(OAc)₂/CsF/DMF leads mainly to (E)-(OCH₂CMe₂CH₂O)P(O)CH=C(Me)Ph (21) and (OCH₂CMe₂CH₂O)P(O)CH₂-C(Ph)=CH₂ (22) and is thus a net 1,2-addition of Ph-H. Compound 1b reacts with iodophenol in the presence of Pd(OAc)₂/PPh₃/K₂CO₃ to give a benzofuran that has a structure different from that obtained by using 1c under similar conditions. Treatment of 1a with iodophenol/Pd(OAc)₂/CsF/DMF also gives a benzofuran whose structure is different from that obtained by using 2a under similar conditions. In the reaction with 2-iodobenzoic acid, 1a and 2c afford one type of isocoumarin, while 1b,c and 2a,b give a second type of isocoumarin. The structures of key compounds are established by X-ray crystallography. Utility of the phosphonate products in the Horner-Wadsworth-Emmons reaction is demonstrated.