Keywords: Asymmetric catalysis / Copper / Phosphoramidite / Chirality / Conjugate addition New P-stereogenic phosphoramidites based on a (-)-pinane framework were synthesized and investigated by NMR spectroscopic methods and single-crystal X-ray structural analysis. The reaction between cis-pinandiol 2 and N,N-dialkylphosphoramidous dichlorides, followed by protection with the BH 3 ·THF adduct, afforded diastereomeric mixtures of P S and P R BH 3 -phosphoramidite complexes. After separation by column chromatography, these stereoisomers were obtained in a pure form. The BH 3 group was further cleaved by treatment
g-Pyrone (1) is readily accessible in 59% overall yield via 1,1,5,5-tetraethoxy-3-pentanone (10b) and subsequent acidic hydrolysis. The synthesis enables an easy scale up, as demonstrated for intermediate 10b.
Chiral bisphosphinites 5 were obtained by dihydroxylation of (-)-a-pinene (1) followed by deprotonation and treatment with chlorophosphines 3. Unlike their corresponding borane adducts 4, compounds 5 turned out to be very sensitive.Among the chiral building blocks for the synthesis of phosphane and phosphinite ligands, 1,2 terpenes have received increasing attention, because the chiral precursors are readily available and can be modified conveniently. Whereas camphor-derived ligands have been widely used, 3-10 the corresponding ligands based on pinene have been only rarely explored. 11,12 This is surprising because both enantiomers of a-pinene are commercially available at reasonable prices, making a-pinene particularly attractive as a precursor. This prompted us to investigate the suitability of a-pinene for the synthesis of bisphosphinites. The results towards this goal are discussed below.Following a catalytic dihydroxylation procedure by Matteson 13 a-pinene was treated with 0.003 mol% of OsO 4 and 1.4 equivalents of trimethylamine-N-oxide dihydrate in the presence of pyridine in t-BuOH-H 2 O under reflux. Under these conditions the desired diol 2 was obtained diastereoselectively in 65% yield (Scheme 1). No trace of the other diastereomer was found in the crude product.The diol 2 was subsequently deprotonated with 2.2 equivalents of BuLi in THF at -78 °C followed by treatment with chlorophosphines 3a-c (2.2 equiv) under reflux. Protection with BH 3 ·THF afforded the bisphosphinites 4a-c in moderate yields (22-51%), which could be purified by flash chromatography on SiO 2 without any decomposition. However, attempted deprotection of the borane adducts 4 with DABCO 10 failed completely. Instead of the anticipated bisphosphinites 5a-c only phosphane oxides were found, resulting from an Arbuzov-type rearrangement. Therefore, a direct route to the unprotected phosphinites has to be realized. Diol 2 was first deprotonated with triethylamine in toluene at room temperature. Then the respective chlorophosphine 3a-d was added at -78 °C and, depending on the type of chlorophosphine, either stirring at room temperature (for 3a) or heating at reflux was necessary to complete the reaction ( Table 1). Filtration of the crude products through neutral Al 2 O 3 yielded the bisphosphinites 5a-d. The products 5b,c with two alkyl substituents at the phosphorus atom, however, proved to be very oxygen sensitive. The tert-butyl derivative 5c decomposed completely during the purification step and the dicyclohexyl phosphinite 5b could be isolated in only 3% yield. In contrast, the diphenyl derivative 5a and the mixed phenyl tert-butyl phosphinite 5d were obtained in 43% and 25% yields, respectively. The mixed phenyl tertbutyl chlorophosphine 3d was prepared in 45% yield following a known procedure 14 slightly modified by inverse Grignard reaction.In conclusion, a convenient two-step reaction to chiral bisphosphinites 5 starting from (-)-a-pinene (1) was developed. Application of these novel ligands in catalytic reaction is still unde...
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