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Synlett 2004(1): 134-136  
DOI: 10.1055/s-2003-43347
LETTER
© Georg Thieme Verlag Stuttgart · New York

Enantiospecific Synthesis of 9,10-Dihalocamphors

Antonio García Martínez*a, Enrique Teso Vilarb, Amelia García Fraileb, Santiago Moya de la Cerero*a, Cristina Díaz Morillob, Rocío Pérez Morilloa
a Departamento de Química Orgánica I, Facultad de Químicas, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain
Fax: +34(91)3944103; e-Mail: santmoya@quim.ucm.es;
b Departamento de Química Orgánica y Biología, Facultad de Ciencias, UNED, Senda del Rey 9, 28040 Madrid, Spain
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Publication History

Received 7 October 2003
Publication Date:
26 November 2003 (online)

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Abstract

A new, general and straightforward method for the enantiospecific synthesis of 9,10-dihalocamphors (including mixed derivatives) is reported and exemplified for the preparation of (+)-9,10-dibromocamphor (a well-known chiral intermediate) as well as (+)-9-bromo-10-chlorocamphor and (+)-9-bromo-10-iodocamphor (novel mixed dihalides). Our approach is based on a key stereocontrolled tandem electrophilic addition - Wagner-Meerwein rearrangement of optically pure 3-endo-(halomethyl)-3-methyl-2-methylenenorbornan-1-ols, which are easily obtained from readily accessible 9-halocamphors.

Key words

halides - ketones - electrophilic additions - chirality - bicyclic compounds

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9

Treatment of commercial enantiopure 3-endo-,9-dibromocamphor with Zn-HOAc (standard conditions, see ref. [2] ) produces the selective removal of the C(3)-bromine, giving place to pure 1(Br/H) in 95% yield.

10

The reaction of 1(Br/H) with Tf2O was realized under the standard conditions described by us for other related 2-norbornanones (ref. [8] ). After chromatography (silica gel and hexane), pure triflate 5(Br) was obtained as a colorless liquid in 77% yield. [α]D 20 -55.5 (c 1.96, CH2Cl2). 1H NMR and 13C NMR, IR and MS agree with the structure.

11

Alcohol 6(Br) was obtained by standard treatment of 5(Br) with LAH (e.g. ref. [8] ). Purification by chromatography (silica gel and CH2Cl2/Et2O 95:5) yields pure alcohol 6(Br) as a colorless solid in 78% yield. Mp 72-74 °C. [α]D 20 -57.3 (c 0.67, CH2Cl2). 1H NMR and 13C NMR, IR and MS agree with the structure.

12

A solution of 6(Br) and an excess of corresponding N-halosuccinimide (NYS) in CH2Cl2 was stirred at r.t. overnight. After standard work up and purification by chromatography (silica gel and hexane/CH2Cl2 6: 4), corresponding pure 1(Br/Y) was obtained as a colorless solid. Compound 1(Br/Br): 85% yield. Characterization data agree with the previously described in ref. [6b] Compound 1(Br/Cl): 83 yield. Mp 64-66 °C. [α]D 20 +88.6 (c 0.98, CH2Cl2). 1H NMR (200 MHz, CDCl3): δ = 3.86 (d, J = 12.7 Hz, 1 H), 3.71 (d, J = 10.7 Hz, 1 H), 3.66 (d, J = 12.7 Hz, 1 H), 3.56 (d, J = 10.7 Hz, 1 H), 2.59 (dd, J = 4.5 Hz, J = 4.5 Hz, 1 H), 2.48-2.25 (m, 2 H), 2.14-1.93 (m, 1 H), 1.98 (d, J = 18.5 Hz, 1 H), 1.61-1.38 (m, 2 H), 1.12 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 214.2, 62.7, 52.2, 42.3, 41.2, 41.1, 39.9, 25.8, 24.8, 16.9 ppm. IR (CCl4): ν = 2964, 1747, 1415, 1385 cm-1. MS: m/z (%) = 185 (3) [M+ - 79], 171 (31), 121 (24), 107 (100), 93 (31), 79 (42), 39 (50). HRMS: calcd for C10H14BrClO: 263.9916. Found: 263.9915. Compound 1(Br/I): 80% yield. Mp 120-122 °C. [α]D 20 +44.9 (c 0.72, CH2Cl2). 1H NMR (200 MHz, CDCl3): δ = 3.67 (dd, J = 10.5 Hz, J = 1.0 Hz, 1 H), 3.55 (d, J = 10.5 Hz, 1 H), 3.44 (d, J = 11.2 Hz, 1 H), 3.17 (d, J = 11.2 Hz, 1 H), 2.61 (dd, J = 4.4 Hz, J = 4.4 Hz, 1 H), 2.40 (dm, J = 18.5 Hz, 1 H), 2.23-1.91 (m, 2 H), 1.98 (d, J = 18.5 Hz, 1 H), 1.70-1.43 (m, 2 H), 1.07 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3):
δ = 214.0, 60.8, 52.4, 42.0, 41.5, 39.4, 29.5, 26.1, 16.8, 0.3 ppm. IR (CCl4): ν = 2962, 1745, 1456, 1058 cm-1. MS: m/z (%) = 231 (10) [M+·- 127], 229 (9), 189 (4), 187 (4), 149 (6), 121 (70), 107 (100), 93 (45), 79 (60), 67 (22), 41 (58). HRMS: calcd for C10H14BrIO: 355.9273. Found: 355.9269.