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. 2005 Jul 18;46(29):4911-4914.
doi: 10.1016/j.tetlet.2005.04.146.

Stereoselective synthesis of the C(1)-C(13) segment of dolabelide B

Gary E Keck  1 , Mark D McLaws
Affiliations

Stereoselective synthesis of the C(1)-C(13) segment of dolabelide B

Gary E Keck et al. Tetrahedron Lett. .

Abstract

The efficient construction of the C(1)-C(13) segment of dolabelide B is described. A key element of the synthesis entails BITIP catalyzed asymmetric methallylation to establish the C(7) stereocenter, which was then used to direct the stereoselective installation of the C(9) and C(11) centers through Evans reduction and 1,5-anti aldol condensation, respectively.

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Figures

Scheme 1
Scheme 1
Retrosynthetic analysis of dolabelide B.
Scheme 2
Scheme 2
Reagents and conditions: (a) (Z)-crotyltributyltin, TiCl4, −90 °C, 2.5 h, 80% (15:1 dr); (b) TBSOTf, Et3N, CH2Cl2, −30 to 0 °C, 1 h, 83%; (c) O3, CH2Cl2, −78 °C, 15 min; PPh3, rt, 2 h; (d) (C6H5)3P = CHCO2C2H5, CH2Cl2, rt, 18 h; (e) SmI2, MeOH, DMA, 0 °C, 15 min, 55% (three steps); (f) DIBAL, THF, −78 °C, 4 h; (g) (COCl)2, DMSO, Et3N, −78 °C, 4 h, 83% (two steps).
Scheme 3
Scheme 3
Hydroformylation of 7.
Scheme 4
Scheme 4
C7–C8 bond construction via 1,5-anti aldol condensation.
Scheme 5
Scheme 5
Reagents and conditions: (a) (R)-(+)-1,1′-bi-2-naphthol, Ti(OiPr)4,4 Å MS, CH2Cl2, −20 °C, 5 days, 96% (94:6 dr); (b) NaH, p-methoxybenzyl bromide, KI, THF, 0 °C, 6 h, 91%; (c) OsO4, NMO, t-BuOH/THF/H2O, rt, 1.5 h; NaIO4, rt, 2 h, 89%; (d) (C6H11)2BCl, Et3N, Et2O, −78 to −20 °C, 22 h.
Scheme 6
Scheme 6
Reagents and conditions: (a) acrolein, (C6H11)2BCl, Et3N, Et2O, −78 to −20 °C, 22 h, 83% (single isomer); (b) TBSOTF, 2,6-lutidine, THF, 0 °C, 1 h, 96%; (c) DDQ, 10:1 CH2Cl2/pH 7 buffer, 0 °C, 40 min, 89%; (d) Me4NBH(OAc)3, 1:1 acetonitrile/AcOH, −15 °C, 5 h, 85%; (e) Ac2O, DMAP, pyridine, rt, 18 h, 94%.
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References

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