Allyl bromide → 6-Phenyl-hex-3-ynal

HRID 353278Notes

Reaction equation

HRID 353278 reaction equation
[C:1]1([CH2:7][CH2:8][C:9]#[CH:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Br)C=C.[OH-].[K+].C[N+]1([O-])CC[O:21][CH2:20][CH2:19]1>[N+](CCCC)(CCCC)(CCCC)CCCC.[Cl-].O=[Os](=O)(=O)=O.O.C(Cl)Cl>[C:1]1([CH2:7][CH2:8][C:9]#[C:10][CH2:19][CH:20]=[O:21])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

9

Reactant 4

HCID 7841Allyl bromideHCID 14797Potassium HydroxideHCID 82029Methyl morpholine oxideHCID 1233604-Phenyl-1-butyne

Product 1

HCID 220588076-Phenyl-hex-3-ynal

Reagents, catalysts & solvents 4

HCID 30318Osmium TetroxideCatalystHCID 70681Tetrabutylammonium ChlorideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

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. Sequental 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.

Workup

  1. customcommercially available from Lancaster Synthesis, Windham, N.H

Sources & evidence

ORD record
ord-003371ee16f44694aa8c298d145c3c3f
Source dataset
uspto-grants-2004_06
Patent number
US06750250B1

Reaction notes

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