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Synlett 2003(15): 2313-2316  
DOI: 10.1055/s-2003-42124
LETTER
© Georg Thieme Verlag Stuttgart · New York

Highly Diastereoselective Synthesis of Manoyl Oxide Derivatives by TiCl4-Catalyzed Nucleophilic Cleavage of Ambracetal Derivatives

A. F. Barrero*, E. J. Alvarez-Manzaneda Roldán*, J. L. Romera Santiago, R. Chahboun
Departamento de Química Orgánica, Facultad de Ciencias, Instituto de Biotecnología, Universidad de Granada, 18071 Granada, Spain
Fax: +34(958)246387; e-Mail: eamr@ugr.es;
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Publication History

Received 24 July 2003
Publication Date:
07 November 2003 (online)

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Abstract

The treatment of acetal 11 with KCN and AlCNEt2 in the presence of TiCl4 produces in high diastereoselectivity 2-cyanooxane 14, which can be easily converted into manoyl oxide derivatives. Using this strategy, 19-hydroxymanoyl oxide 20, diterpene from P. viscosum, was prepared from communic acids 7a-c after an 8-steps sequence in a 17% overall yield.

Key words

natural products - acetal cleavage - manoyl oxides - Lewis acids - labdane diterpenes

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Typical Procedure for the Nucleophilic Cleavage of 11; Synthesis of Oxanes 14 and 15: To a stirred solution of 11 (0.25 g, 0.78 mmol), 18-crown-6-ether (0.57 g, 2.14 mmol) and KCN (0.2 g, 3.10 mmol) in CH2Cl2 (15 mL), was added AlCNEt2 (1.0 M in CH2Cl2, 6.2 mL) and TiCl4 (1.0 M in CH2Cl2,1.9 mL) at -78 ºC, under Ar atmosphere. The reaction mixture was then stirred at the indicated temperature during the time showed in Table [2] . Then an aq 1 M NaHCO3 solution (8 mL) was added and the resulting mixture was stirred for 3 h, and extracted with t-BuOMe (2 × 30 mL). The organic phase was successively washed with 5% aq NaHCO3 (2 × 30 mL), water (2 × 30 mL), brine (2 × 30 mL), dried over anhyd Na2SO4 and evaporated to give a crude product which was chromatographed (hexane- t-BuOMe, 3:2) to yield 14 and 15.

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All new compounds were fully characterized spectroscopically and had satisfactory HRMS data.
Selected data:
Compound 14: 1H NMR (400 MHz, CDCl3): δ = 0.58 (s, 3 H, Me-10a), 1.04 (dc, J = 13.7, 4.2 Hz, 2 H), 1.16 (s, 3 H, Me-7), 1.20-1.54 (m, 2 H), 1.57 (s, 3 H, Me-3), 1.65-2.30 (m, 11 H), 3.40 (dd, J = 11.1, 1.5 Hz, 1 H, 4a-CH2OH-A), 3.60 (s, 3 H, 7-COOMe), 3.61 (d, J = 11.6 Hz, 1 H, 4a-CH2OH-B).
13C NMR (100 MHz, CDCl3): δ = 177.4 (7-COOCH3), 122.4 (3-CN), 79.3 (C-4a), 66.8 (C-3), 63.7 (4a-CH2OH), 56.3* (C-10b), 51.3 (7-COOMe), 48.3* (C-6a), 43.7 (C-7), 38.8 (C-10), 37.9 (C-10a), 37.7 (C-8), 36.6 (C-6), 31.9 (C-2), 29.2 (Me-3), 28.5 (Me-7), 21.2 (C-5), 18.9 (C-9), 14.4 (C-1), 12.7 (Me-10a).
Compound 18: 1H NMR (400 MHz, CDCl3): δ = 0.57 (s, 3 H, Me-20), 0.88 (dt, J = 13.3, 4.1 Hz, 1 H), 0.98 (dt, J = 12.9, 3.9 Hz, 1 H), 1.00-1.25 (m, 1 H), 1.17 (s, 3 H, Me-18), 1.28 (s, 3 H, Me-16), 1.65-1.95 (m, 7 H), 2.16 (d, J = 13.1 Hz, 1 H), 2.23 (dt, J = 12.7, 3.4 Hz, 1 H), 3.56 (dd, J = 10.5, 1.7 Hz, 1 H, 17-CH2OH-A), 3.62 (d, J = 10.5 Hz, 1 H, 17-CH2OH-B), 3.62 (s, 3 H, 19-COOMe), 4.99 (dd, J = 10.8, 1.1 Hz, 1 H, =CH2), 5.20 (dd, J = 17.4, 1.1 Hz, 1 H, =CH2), 5.93 (dd, J = 17.4, 10.8 Hz, 1 H, -CH=).
13C NMR (100 MHz, CDCl3): δ = 177.7 (19-COOCH3), 146.7 (C-14), 111.4 (C-15), 77.1 (C-8), 74.4 (C-13), 63.2 (C-17), 56.9* (C-9), 51.4* (C-5), 51.3 (19-COOMe), 43.8 (C-4), 40.0 (C-1), 38.1 (C-3), 37.8 (C-10), 37.7 (C-6), 33.0 (C-12), 30.0 (C-14), 28.6 (C-18), 21.5 (C-7), 19.1 (C-2), 15.1 (C-11), 13.0 (C-20).