Synthesis of Enantiomerically Pure Cyclopropyl Trifluoroborates

Abstract

Enantiomerically pure cyclopropylboronic esters were converted to the corresponding trifluoroborates, versatile inter­mediates for a variety of transformations. The new deprotection conditions allowed the utilization of general building blocks for ­cyclopropyl amines.

Key words

boron - stereoselectivity - protecting groups - cyclo­propanes - cross-coupling

References and Notes

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9

Using (S,S)-8 or (R,R)-8 as enantiomerically pure ligands did not furnish the product in high selectivity.

12

Representative Procedure - Synthesis of ent -15.
KHF₂ (5.50 g, 70.5 mmol) was placed in a round-bottom flask (caution: use Teflon vessel) and dissolved in MeOH (150 mL). The boronic ester 10 (880 mg, 1.41 mmol), dissolved in a minimum amount of CH₂Cl₂, was added and the mixture heated at 80 °C for 2 d. The solvents were removed under reduced pressure, the remaining colorless solids transferred on a Büchner funnel and washed with Et₂O. The product was dissolved in MeCN, the solvent removed under reduced pressure, and the remaining solid recrystallized from MeCN (10 mL). Yield: 92% (345 mg, 1.29 mmol); [α]_D ²⁰ -16.4 (c 0.5, DMSO); mp 197 °C. Anal. Calcd for C₁₁H₁₃BF₃KO (268.12): C, 49.27; H, 4.89. Found: C, 48.82; H, 4.87. ¹H NMR (400 MHz, DMSO-d ₆): δ = -0.87 (ddd, ³ J _1,3a = 9.8 Hz, ³ J _1,3b = 6.7 Hz, ³ J _1,2 = 3.4 Hz, 1 H, 1-H), -0.16 (ddd, ³ J _3a,1 = 9.8 Hz, ³ J _3a,2 = 3.3 Hz, ² J _3a,3b = 2.9 Hz, 1 H, 3-H_a), 0.09 (ddd, ³ J _3b,2 = 6.8 Hz, ³ J _3b,1 = 6.7 Hz, ² J _3b,3a = 2.9 Hz, 1 H, 3-H_a), 0.79 (m_c, 1 H, 2-H), 3.07 (dd, ² J _4a,4b = 10.2 Hz, ³ J _4a,2 = 7.3 Hz, 1 H, 4-H_a), 3.30 (dd, ² J _4b,4a = 10.2 Hz, ³ J _4b,2 = 6.1 Hz, 1 H, 4-H_b), 4.61 (d, ² J = 12.2 Hz, 1 H, Bn-H_a), 4.68 (d, ² J = 12.2 Hz, 1 H, Bn-H_b), 7.25-7.34 (m, 5 H, arom.-H) ppm. ¹³C NMR (100 MHz, DMSO-d ₆): δ = 6.9 (C-3), 13.6 (C-2), 70.6 (Bn-CH₂), 76.4 (C-4), 126.9, 127.2, 128.0 (CH_arom), 139.1 (C _arom) ppm. ¹⁹F NMR (400 MHz, DMSO-d ₆): δ = -140.06 (s, 3 F, BF ₃) ppm.

15

CCDC-297716 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone]; email: [e-mail]].