Allyl bromide → 6-Phenyl-hex-3-ynal

Participants

Reaction Steps

Reaction of 4-phenyl-1-butyne (5; commercially available from Lancaster Synthesis, Windham, N.H.) with allyl bromide under phase-transfer conditions (CH2Cl2, n-BU4NCl, water, KOH), selective oxidation of the alkene moiety using catalytic OsO4/pyr and stoichiometric N-methylmorpholine-N-oxide, and oxidative cleavage of the resultant diol using NalO4 affords 6-phenyl-hex-3-ynal (6). Lithiation of phosphine oxide 7 [Katritzky, Alan R., Feng, Daming, Lang, Hengyuan J. Org. Chem., volume 62(12) page 4131 (1997)], Wittig condensation with 6, and heating of the intermediate dienyne (not shown) with p-toluenesulfonic acid in ethanol affords enyne 8. Asymmetric dihydroxylation of 8 with AD mix α (Aldrich Chemical Co., Milwaukee) and methanesulfonamide [Sharpless, K. B., Amberg, W., Bennani, Y. Crispino, G. A.; Hartung, J; Jeong, K. S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.; Xu, D. Zhang, X.-L. J. Org. Chem., volume 57, page 2768 (1992)], followed by selective reduction with H2 over Pd/BaSO4, affords β-hydroxy lactone 9. Sequential treatment of 9 with CH3SO2Cl/NEt3 and diisobutylaluminum hydride (DIBAL-H) provides lactol 10. Sodium borohydride reduction, K2CO3 treatment, and oxidation of the resulting β-hydroxyepoxide with the Dess-Martin reagent produces the epoxyaldehyde 11. Wittig olefination of 11 and known ylide 12 [Zamboni, R.; Milettee, S.; Rokach, J. Tetrahedron Lett., volume 24, page 4899 (1983)] followed by saponification of the resulting methyl ester with LiOH in dimethoxyethane (DME)/water yields 2.

Provenance & Evidence