Application of a Stereoselective Rhodium(II)-Catalyzed Oxonium Ylide Formation–[2,3]-Sigmatropic Rearrangement of an α-Diazo-β-keto Ester to the Synthesis of 2-epi-Cinatrin C₁ Dimethyl Ester

Abstract

The Rh₂(OAc)₄-catalyzed oxonium ylide formation–[2,3]-sigmatropic rearrangement of a highly functionalized α-diazo-β-keto ester derived from d-glucose proceeded stereoselectively to give the corresponding tetrahydrofuran-3-one as a single diastereomer in high yield. This reaction was applied to the synthesis of 2-epi-cinatrin C₁ dimethyl ester as a key step.

Key words

diazoketo ester - rhodium(II) catalyst - oxonium ylide - [2,3]-sigmatropic rearrangement - cinatrin

• References

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• 7 Rhodium(II)-Catalyzed Reaction of α-Diazo-β-keto Ester 4: To a solution of Rh₂(OAc)₄ (17 mg, 0.038 mmol) in CH₂Cl₂ (40 mL) was added a solution of 4 (618 mg, 1.27 mmol) in CH₂Cl₂ (24 mL). The resulting solution was refluxed for 8 h. After concentration of the reaction, the residue was purified by column chromatography on SiO₂ (5% EtOAc in hexane) to give 3 (459 mg, 79%) as a colorless oil; [α]_D ²⁶ +12.9 (c = 0.750, CHCl₃). IR (neat): 1781, 1753 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 0.09 (s, 6 H), 0.11 (s, 3 H), 0.18 (s, 3 H), 0.90 (s, 9 H), 0.91 (s, 9 H), 2.61–2.81 (m, 2 H), 3.72 (s, 3 H), 3.82 (dd, J = 11.8, 3.0 Hz, 1 H), 3.91 (ddd, J = 8.9, 3.0, 2.1 Hz, 1 H), 4.00 (dd, J = 11.8, 2.1 Hz, 1 H), 4.57 (d, J = 8.8 Hz, 1 H), 5.11–5.21 (m, 2 H), 5.67–5.81 (m, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = –5.5, –5.4, –5.3, –4.4, 18.2, 18.3, 25.6 (3), 25.8 (3), 38.4, 52.8, 61.3, 72.3, 80.2, 84.8, 120.2, 130.7, 167.6, 208.6. MS: m/z = 459 [M⁺ + H]. HRMS (EI): m/z calcd for C₂₂H₄₃O₆Si₂: 459.2598; found: 459.2578.
• 8 Spectroscopic data for 10: colorless crystals; mp 86–88 °C (from 5% EtOAc in hexane); [α]_D ²¹ −30.8° (c = 0.5, CHCl₃). IR (neat): 1740, 1531 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = −0.04 (s, 3 H), 0.06 (s, 3 H), 0.09 (s, 3 H), 0.10 (s, 3 H), 0.74 (s, 9 H), 0.91 (s, 9 H), 2.74 (dd, J = 14.0, 7.4 Hz, 1 H), 2.89 (dd, J = 13.6, 7.4 Hz, 1 H), 3.70 (dd, J = 11.8, 4.0 Hz, 1 H), 3.73 (s, 3 H), 3.81 (dd, J = 11.3, 3.3 Hz, 1 H), 4.08 (dt, J = 5.2, 3.3 Hz, 1 H), 4.52 (t, J = 4.9 Hz, 1 H), 5.01–5.06 (m, 1 H), 5.08 (br s, 1 H), 5.64–5.79 (m, 1 H), 5.75 (d, J = 4.9 Hz, 1 H), 8.25 (d, J = 8.8 Hz, 2 H), 8.32 (d, J = 8.8 Hz, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = −5.53, −5.46, −5.1, −5.0, 17.7, 18.4, 25.5 (3), 25.9 (3), 38.4, 52.4, 62.4, 71.4, 84.9, 86.2, 119.0, 123.7, 130.8, 131.6, 135.2, 160.7, 163.5, 171.7. MS: m/z = 610 [M⁺ + H]. HRMS (EI): m/z calcd for C₂₉H₄₈O₉NSi₂: 610.2867; found: 610.2868. The X-ray data are now being deposited with the CCDC. CCDC-908929 (for 10) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.�
• 9 The coupling constant between the olefinic protons of 11 was observed to be 15.4 Hz.
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• 12 Spectroscopic data for 2: a colorless oil; [α]_D ¹⁸ −35.1° (c = 0.750, CHCl₃). IR (neat): 3462, 1806, 1748 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 0.88 (t, J = 6.6 Hz, 3 H), 1.25 (br s, 20 H), 1.92 (ddd, J = 14.0, 11.8, 4.4 Hz, 1 H), 2.08 (ddd, J = 14.0, 11.8, 4.4 Hz, 1 H), 2.93 (d, J = 9.1 Hz, 1 H), 3.79 (s, 3 H), 3.86 (s, 3 H), 3.89 (br s, 1 H), 4.99 (d, J = 8.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 14.1, 22.6, 23.2, 29.3, 29.4, 29.56, 29.60, 30.7, 31.9, 53.3, 54.0, 71.3, 81.3, 89.2, 168.9, 169.1, 172.7. MS: m/z = 402 [M⁺]. HRMS (EI): m/z calcd for C₂₀H₃₄O₈: 402.2254; found: 402.2234.
• 13 Unfortunately, the treatment of 2 with aqueous sodium hydroxide according to Rizzacasa’s cinatrin syntheses (see refs. 5a and 5b) gave a complex mixture. It is very interesting that the stereochemistry of the C-2 position strongly influenced its chemical stability.