Several chiral 2-bromo-6-alkoxypyridines (2) were prepared from the treatment of 2,6-dibromopyridine with the appropriate potassium alkoxide (alkoxides used: methoxide, myrtanoxide, myrtenoxide, iso-pinocampheoxide, isomenthoxide, fenchoxide, and borneoxide) in dimethylformamide at 80 °C for 30 miN. C.ompound 2 was found to undergo facile halogen-metal exchange with n-BuLi in THF at -78 °C to afford the 2-lithio-6-alkoxypyridines (3). Treatment of 3 with R2SiCl2 resulted in formation of the novel bis-(pyridyl)silane compounds [2-(6-alkoxypyridyl)]2SiR2 (4, R = Me; 5, R = Ph) in excellent yield. The latter compounds readily chelated to palladium(II) chloride to form air-stable complexes, {[2-(6-alkoxy-pyridyl)]2SiR2}PdCl2 (6, R = Me; 7, R = Ph). The palladium complexes were fully characterized by spectroscopic and analytical data. Oxidative coupling of compounds 3 with copper(I) iodide and oxygen at -78 °C afforded the new 6,6ʹ-dialkoxy2,2ʹ-bipyridines (8) in 34-38% isolated yields. Treatment of 3 with dimethylformamide produced a new series of optically pure 6-alkoxy-2-pyridinecarboxaldehydes (9) in greater than 90% isolated yield. Subsequent reaction of 9 with 3 afforded the bis[2-(6-alkoxy-pyridyl)] methanol ligands (10) in excellent yield. Compound 10 was O-alkylated (NaH, DMF) with benzyl chloride to afford 11. The benzylated compound 11 was complexed to palladium (II) chloride and found by NMR spectroscopy to exist as one of the two possible boat conformations. The energy barriers for rotation about the benzyl-oxygen bond in the latter complexes were found to be dependent upon the chiral alkoxy group on the pyridine ring. Ligand 10 was attached to cross-linked polystyrene beads with 56-74% modification of the chloromethyl sites. Further modification of the remaining chloromethyl reaction sites to hydroxymethyl groups was accomplished by treatment of the polymer with methanolic potassium hydroxidE. C.omplete incorporation of the ligand was achieved by utilizing a lower loading of chloromethyl sites (0.75 mequiv/g) in the starting polymer. Treatment of 2-pyridinecarboxaldehyde with 3 resulted in the two diastereoisomeric products, [2-(6-alkoxypyridyl)](2-pyridyl)methanol (17): in the case of R*O = (1S,2R,4S)-borneoxy the isomers could not be separated; however, when R*O = (lR,2R,4S)-l,3,3-trimethyl-2-norborneoxy the isomers 17(i) and 17(ii) were easily separated by column chromatography. Selected ligands prepared in the study were used in the rhodium-catalyzed hydrosilation (Ph2SiH2) of acetophenonE. C.hemical yields were ~85%, and optical yields ranged from 0 to 12.7% for the hydrosilations and 0.5 to 10.0% for the asymmetric cyclopropanation of 2,5-dimethyl-2,4-hexadiene. © 1990, American Chemical Society. All rights reserved.
