Enantiopure Dicyclopropanes
from trans-Cyclohexadienediols

Tobias Hausmann; Jörg Pietruszka

doi:10.1055/s-0029-1218360

LETTER

Enantiopure Dicyclopropanes from trans-Cyclohexadienediols

Tobias Hausmann, Jörg Pietruszka*
Institut für Bioorganische Chemie, Heinrich-Heine Universität Düsseldorf im Forschungszentrum Jülich, Stetternicher Forst Geb. 15.8, 52426 Jülich, Germany
Fax: +49(2461)616196; e-Mail: j.pietruszka@fz-juelich.de;

Abstract

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Abstract

The protecting-group-induced highly regio- and enantioselective syntheses of dicyclopropanated building blocks starting from microbially produced trans-2,3-dihydroxy-2,3-dihydrobenzoic acid are described. Key to the success was a two-step cycloaddition-photolysis sequence for the second cyclopropanation. The structure of the unexpected inverse [3+2]-cycloaddition product of the 1,3-dipolar cycloaddition was verified.

Key words

asymmetric synthesis - stereoselectivity - trans-cyclohexadienediol - cyclopropanes - 1,3-dipolar cycloaddition

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References

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[3+2]-Dipolar Cycloaddition; General Procedure
A freshly prepared solution of CH₂N₂ [¹7] in Et₂O (0.4 M, 10 equiv) was added to a solution of cyclopropane 4 (1 equiv) in dry Et₂O (6 mL/equiv). After 3 d in the dark at r.t. and without stirring, complete conversion (as judged by TLC) was detected. The excess CH₂N₂ was destroyed, and the mixture was concentrated under reduced pressure. Flash column chromatography on silica gel (eluent: PE-EtOAc, gradient 85:15 to 60:40), provided 9a (84%) as colourless crystals and 9b (15%) as colourless oil.
Selected Data of Regioisomer 9a
^¹H NMR (600 MHz, CDCl₃): δ = 0.67 (m, 1 H, 4-H_a), 0.67 (m, 1 H, 3b-H), 0.76 (m, 1 H, 4-H_b), 1.12 (dddd, ^³ J _4a,4b = 4.4 Hz, ^³ J _4a,4-a = 5.4 Hz, ^³ J _4a,3b = 8.5 Hz, ^³ J _4a,4-b = 8.5 Hz, 1 H, 4a-H), 1.30 (s, 3 H, 6-CH₃), 1.36 (s, 3 H, 7-CH₃), 2.59 (dd, ^³ J _3a,3-a = 1.3 Hz, ^³ J _3a,3-b = 7.6 Hz, 1 H, 3a-H), 3.21 (s, 3 H, 6-OCH₃), 3.30 (s, 3 H, 7-OCH₃), 3.66 (s, 3 H, CO₂CH₃), 3.90 (dd, ^³ J _4b,4a = 4.4 Hz, ^³ J _4b,8a = 10.5 Hz, 1 H, 4b-H), 4.36 (dd, ^² J _3-b,3-a = 17.5 Hz, ^³ J _3-b,3a = 7.6 Hz, 1 H, 3-H_b), 4.37 (d, ^³ J _8a,4b = 10.5 Hz, 1 H, 8a-H), 4.78 (dd, ^² J _3-a,3-b = 17.5 Hz, ^³ J _3-a,3a = 1.3 Hz, 1 H, 3-H_a) ppm. ^¹³C NMR (151 MHz, CDCl₃): δ = 7.6 (C-4), 14.7 (C-4a), 16.2 (C-3b), 18.0 (7-CH₃), 18.1 (6-CH₃), 37.6 (C-3a), 48.0 (6-OCH₃), 48.4 (7-OCH₃), 53.0 (CO₂ CH₃), 63.7 (C-4b), 66.5 (C-8a), 84.9 (C-3), 96.9 (C-8b), 100.0 (C-6), 100.9 (C-7), 169.0 (CO₂CH₃) ppm.
Selected Data of Regioisomer 9b ^¹H NMR (600 MHz, CDCl₃): δ = 0.78 (dddd, ^² J _8-a,8-b = 6.3 Hz, ^³ J _8-a,7b = 8.2 Hz, ^³ J _8-a,8a = 9.4 Hz, ⁴ J _8-a,7a = 0.6 Hz, 1 H, 8-H_a), 1.00 (ddd, ^² J _8-b,8-a = 6.3 Hz, ^³ J _8-b,7b = 5.2 Hz, ^³ J _8-b,8a = 6.3 Hz, 1 H, 8-H_b), 1.17 (s, 3 H, 5-CH ₃), 1.20 (dddd, ^² J _7b,7a = 3.8 Hz, ^³ J _7b,8-b = 5.2 Hz, ^³ J _7b,8-a = 8.2 Hz, ^³ J _7b,8a = 8.7 Hz, 1 H, 7b-H), 1.24 (s, 3 H, 6-CH ₃), 1.86 (dddd, ^³ J _8a,8b = 1.2 Hz, ^³ J _8a,8-b = 5.4 Hz, ^³ J _8a,7b = 8.7 Hz, ^³ J _8a,8-a = 9.4 Hz, 1 H, 8a-H), 3.16 (s, 3 H, 5-OCH₃), 3.18 (s, 3 H, 6-OCH₃), 3.66 (s, 3 H, CO₂CH₃), 3.66 (ddd, ^³ J _7a,7b = 3.8 Hz, ^³ J _7a,3b = 10.4 Hz, ⁴ J _7a,8-a = 0.6 Hz, 1 H, 7a-H), 4.25 (d, ^³ J _3b,7a = 10.4 Hz, 1 H, 3b-H), 4.86 (dd, ^² J _3-b,3-a = 19.4 Hz, ⁴ J _3-b,8b = 3.0 Hz, 1 H, 3-H_b), 5.03 (ddd, ^³ J _8b,8a = 1.2 Hz, ⁴ J _8b,3-a = 1.1 Hz, ⁴ J _8b,3-b = 3.0 Hz, 1 H, 8b-H), 5.13 (dd, ^² J _3-a,3-b = 19.4 Hz, ⁴ J _3-a,8b = 1.1 Hz, 1 H, 3-H_a) ppm. ^¹³C NMR (151 MHz, CDCl₃): δ = 5.3 (C-8), 13.5 (C-8a), 14.4 (C-7b), 17.7 (6-CH₃), 17.9 (5-CH₃), 48.1 (5-OCH₃), 48.2 (6-OCH₃), 50.0 (C-3a), 53.0 (CO₂ CH₃), 63.9 (C-7a), 65.7 (C-3b), 82.1 (C-3), 92.3 (C-8b), 99.8 (C-6), 100.2 (C-5), 173 (CO₂CH₃) ppm.

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