Synthesis of a new chiral source, (1R,2S)-1-Phenylphospholane-2-carboxylic acid, via a key intermediate alpha-phenylphospholanyllithium borane complex: configurational stability and X-ray crystal structure of an alpha-monophosphinoalkyllithium borane complex.
A synthetic route to enantiomerically pure (1R,2S)-1-phenylphospholane-2-carboxylic acid (1), which is a phosphorus analogue of proline, has been established. A key step is the deprotonation-carboxylation of the 1-phenylphospholane borane complex 3 by using sBuLi/1,2-dipiperidinoethane (DPE). Configurational stability of the key intermediate, the amine-coordinated alpha-phosphinoalkyllithium borane complex 4, was investigated by employing lithiodestannylation-carboxylation of both diastereomers of the 1-phenyl-2-trimethylstannylphospholane borane complex 7 in the presence of several kinds of amines, and as a result, 4 was found to be configurationally labile even at -100 degrees C. The key intermediate, the DPE-coordinated trans-1-phenyl-2-phospholanyllithium borane complex 9, was isolated, and the structure was identified by X-ray crystal structure analysis. This is the first X-ray crystal structure determined for an alpha-monophosphinoalkyllithium borane complex. Remarkably, the alkyllithium complex is monomeric and tricoordinate at the lithium center with a slightly pyramidalized environment, and the existence of a Li--C bond (2.170 A) has been confirmed. Moreover, (1)H-(7)Li HOESY and (6)Li NMR analyses suggested the structure of 9 in solution as well as the existence of an equilibrium between 9, its cis isomer, and the ion pair 8 at room temperature, which was extremely biased towards 9 at -100 degrees C. Finally, 1 was used as a chiral ligand in a palladium-catalyzed allylic substitution, and the desired product was obtained in high yield with good enantioselectivity.
Sun
Xiang-Min
XM
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Manabe
Kei
K
Lam
William W-L
WW
Shiraishi
Nobuyuki
N
Kobayashi
Jun
J
Shiro
Motoo
M
Utsumi
Hiroaki
H
Kobayashi
Shu
S
D001880:Boranes / Q000138:chemical synthesis / Q000737:chemistry*; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004355:Drug Stability; D008958:Models, Molecular; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D001880:Boranes; D002264:Carboxylic Acids; D009943:Organophosphorus Compounds