Subscribe to RSS
DOI: 10.1055/s-0029-1219357
1,5-Stereocontrol in Bismuth-Mediated Reactions between Aldehydes and Allyl Bromides: Stereoselective Synthesis of Open-Chain all-syn- and anti, anti-1,3,5-Disposed Trimethylalkanes
Publication History
Publication Date:
02 February 2010 (online)

Abstract
The reaction of 5-benzyloxy-2,4-dimethylpent-2-enyl bromide with the bismuth species generated by reduction of bismuth(III) iodide by zinc powder gives an intermediate which reacts with aldehydes with useful levels of stereocontrol in favour of 1,5-anti-(3E)-5-methylalk-3-enols. Manipulation of protecting groups, stereoselective hydrogenation, and tosylate displacement using a higher-order cyanomethylcuprate leads to either all-syn or anti,anti-1,3,5-disposed trimethylalkanes.
Key words
Aldehydes - organometallic reagents - allylation - hydrogenation - diastereoselectivity
- 1
Thomas EJ. Chemical Rec. 2007, 7: 115 -
2a
Casteno P.Thomas EJ.Weston A. Tetrahedron Lett. 2007, 48: 337 -
2b
Thomas EJ.Weston A. Tetrahedron Lett. 2007, 48: 341 - 3
Wada M.Ohki H.Akiba K.-Y. Bull. Chem. Soc. Jpn. 1990, 63: 1738 -
4a
Donnelly S.Fielding M.Thomas EJ. Tetrahedron Lett. 2004, 45: 6779 -
4b
Donnelly S.Thomas EJ.Arnott EA. Chem. Commun. 2003, 1460 - 5
Zhou J.Zhu Y.Burgess K. Org. Lett. 2007, 9: 1391 -
6a
Herber C.Breit B. Angew. Chem. Int. Ed. 2005, 44: 5267 -
6b
Herber C.Breit B. Eur. J. Org. Chem. 2007, 3512 - 7
Zhu G.Liang B.Negishi E.-i. Org. Lett. 2008, 10: 1099 - 8
ter Horst B.Feringa BL.Minnaard A. Org. Lett. 2007, 9: 3013 - 10
Teerawutgulrag A.Thomas EJ. J. Chem. Soc., Perkin Trans. 1 1993, 2863 - 12
Trost BM.Belletire JL.Godleski S.McDougal PG.Balkovec JM.Baldwin JJ.Christy ME.Ponticello [nl]GS.Varga SL.Springer JP. J. Org. Chem. 1986, 51: 2370 -
13a
Evans DA.Morrissey MM. Tetrahedron Lett. 1985, 26: 6005 -
13b
Evans DA.Morrissey MM. J. Am. Chem. Soc. 1984, 106: 3866 - 14
Brown JM. Angew. Chem., Int. Ed. Engl. 1987, 26: 190 - 15
Lipshutz BH.Wilhelm RS.Kozlowski JA. Tetrahedron 1984, 40: 5005 - 16
Chow S.Fletcher MT.Lambert LK.Gallagher OP.Moore CJ.Cribb BW.Allsopp PG.Kitching W. [nl]J. Org. Chem. 2005, 70: 1808
References and Notes
(R)-6: [α]D �5 -13.9 (c 0.0046, CHCl3).
11Zinc powder (30 mg, 0.46 mmol) was added to a solution of bismuth(III) iodide (234 mg, 0.4 mmol) in THF (1.65 mL) and the mixture stirred at r.t. for 1 h. The pent-2-enyl bromide 6 (75 mg, 0.26 mmol) and benzaldehyde (27 �L, 0.26 mmol) in THF (0.6 mL) were added and the mixture heated under reflux for 2 h. After cooling, the mixture was filtered and concentrated under reduced pressure. Column chromatography of the residue gave (1S,5R,3Z)-6-benzyl-oxy-3,5-dimethyl-1-phenylhex-3-en-1-ol (9a, 8 mg, 10%), as an oil. R f = 0.28 (light PE-Et2O, 3:1). HRMS: m/z calcd for C21H30O2N: 328.2271 [M]; found: 328.2273 [M + NH4]. IR: νmax = 3414, 1453, 1088, 1026, 752, 699 cm-�. �H NMR (300 MHz, CDCl3): δ = 0.83 (3 H, d, J = 7 Hz, 5-CH3), 1.90 (3 H, d, J = 1 Hz, 3-CH3), 2.22 (1 H, dd, J = 14, 3 Hz, 2-H), 2.78 (1 H, dd, J = 14, 10 Hz, 2-H′), 2.83 (1 H, m, 5-H), 3.18 (1 H, t, J = 9 Hz, 6-H), 3.41 (1 H, dd, J = 9, 5 Hz, 6-H′), 4.55 and 4.58 (each 1 H, d, J = 12 Hz, OHCHPh), 4.87 (1 H, dd, J = 10, 3 Hz, 1-H), 5.18 (1 H, dd, J = 10, 1 Hz, 4-H), 7.38 (10 H, m, ArH). ��C NMR (75 MHz, CDCl3): δ = 17.6, 23.8, 33.2, 43.6, 71.4, 73.3, 75.2, 125.9, 127.2, 128.0, 128.3, 128.5, 128.7, 132.6, 133.0, 138.2, 145.7. MS (CI): m/z (%) = 328 (18) [M+ + 18], 310 (9) [M+], 293 (41), 99 (100). [nl]The second fraction off the column was a mixture of the (1R,5R,3E)- and (1S,5R,3E)-6-benzyloxy-3,5-dimethyl-[nl]1-phenylhex-3-en-1-ols 7a and 8a (53 mg, 65%) as a colourless oil; 1,5-anti-7a/1,5-syn-8a = 93:7, R f = 0.25 (light PE-Et2O, 3:1). HRMS: m/z calcd for C21H30O2N: 328.2271 [M]; found: 328.2273 [M+ + NH4]. IR: νmax = 3431, 1603, 1453, 1374, 1089, 750, 649 cm-�. �H NMR (300 MHz, CDCl3): δ (major isomer) = 0.98 (3 H, d, J = 7 Hz, 5-CH3), 1.77 (3 H, d, J = 1 Hz, 3-CH3), 2.33 (1 H, dd, J = 13, 9 Hz, 2-H), 2.44 (1 H, dd, J = 13, 4 Hz, 2-H′), 2.82 (1 H, m, 5-H), 3.30 (1 H, dd, J = 9, 8 Hz, 6-H), 3.34 (1 H, dd, J = 9, 6 Hz, 6-H′), 4.55 and 4.59 (each 1 H, d, J = 12 Hz, OHCHPh), 4.77 (1 H, dd, J = 10, 4 Hz, 1-H), 5.13 (1 H, dd, J = 9, 1 Hz, 4-H), 7.39 (10 H, m, ArH). ��C NMR (75 MHz, CDCl3): δ = 16.6, 17.5, 33.5, 51.0, 71.0, 73.3, 75.4, 126.1, 127.5, 127.8, 127.9, 128.5, 128.6, 132.4, 133.1, 138.7, 144.4; δ (minor isomer) = 1.04 (3 H, d, J = 7 Hz, 5-CH3). MS (CI): m/e (%) = 328 (59) [M+ + 18], 310 (71) [M+], 293 (84), 99 (100).