Conjugate Addition Routes to 2‐alkyl‐2,3‐dihydroquinolin‐4(1H)‐ones and 2‐alkyl‐4‐hydroxy‐1,2‐dihydroquinoline‐3‐carboxylates

Under CuBr center dot SMe2/PPh3 catalysis (5/10 mol-%) RMgCl (R = Me, Et, nPr, CH=CH2, nBu, iBu, nC(5)H(11), cC(6)H(11), Bn, CH2Bn, nC(11)H(23)) readily (-78 degrees C) undergo 1,4-addition to Cbz or Boc protected quinolin-4(1H)-ones to provide 2-alkyl-2,3-dihydroquinolin-4(1H)-ones (14 examples, 54-99 % yield). Asymmetric versions require AlEt3 to Boc-protected ethyl 6-substituted 4(1H)-quinolone-3-carboxylates (6-R group = all halogens, n/i/t-alkyls, CF3) and provide 61-91 % yield, 30-86 % ee; any halogen, Me, or CF3 provide the highest stereoselectivities (76-86 % ee). Additions of AlMe3 or Al(nC(8)H(17))(3) provide approximate to 45 and approximate to 75 % ee on addition to the parent (6-R = H). Ligand (S)-(BINOL)P-N(CHPh2)(cC(6)H(11)) provides the highest ee values engendering addition to the Si face of the 4(1H)-quinolone-3-carboxylate. Allylation and deprotection of a representative 1,4-addition product example confirm the facial selectivity (X-ray crystallography).