Titanium-Mediated Cyclopropanation
on Diesters: Mechanistic Study on the Dramatic Effects of Selected
Parameters

Mouhamad Jida; Xavier Gaucher; Jean Ollivier

doi:10.1055/s-0029-1220125

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Synlett 2010(11): 1627-1630
DOI: 10.1055/s-0029-1220125

LETTER

Titanium-Mediated Cyclopropanation on Diesters: Mechanistic Study on the Dramatic Effects of Selected Parameters

Mouhamad Jida, Xavier Gaucher, Jean Ollivier*
Laboratoire de Synthèse Organique et Méthodologie, UMR 8182, Institut de Chimie Moléculaire et des Matériaux d’Orsay, Université de Paris-Sud XI, 91405 Orsay, France
Fax: +33(1)69157252; e-Mail: jean.ollivier@u-psud.fr;

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Publication History

Received 5 April 2010
Publication Date:
01 June 2010 (online)

Abstract
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Abstract

Competitive reactions of diisopropyloxy(η^²-alkene)titanium on N-allyl diesters derived from natural amino acids and performed under varying conditions (temperature, nature, and concentration of Grignard reagents) show different regio- and chemoselectivities. In light of the isolated reaction products, a possible mechanism of the formation of original products is discussed.

Key words

esters - fused ring systems - heterocycles - regioselectivity - titanium - Kulninkovich reaction

References and Notes

1 Garnier J.-M. Jida M. Ollivier J. Synlett 2006, 2739

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4 Jida M. PhD Thesis Université de Paris-Sud 11; France: 2008.

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7

Selected Data
tert -Butyl 3-{3-Benzyl-1-hydroxy-3-azabicyclo-[3.1.0]hex-2-yl} Propanoate (5)
Colourless liquid. IR (neat): 3333, 3027, 2931, 1740, 1602 cm^-¹. ^¹H NMR (360 MHz, CDCl₃): δ = 7.34-7.24 (m, 10 H, cis + trans), 5.18-5.01 (m, 2 H, cis + trans), 4.09 (d, J = 13.7 Hz, 1 H, cis), 4.00 (d, J = 13.3 Hz, 1 H, trans), 3.86 (d, J = 13.7 Hz, 1 H, cis), 3.75 (d, J = 13.3 Hz, 1 H, trans), 3.23 (dd, J = 12.6, 6.1 Hz, 1 H, cis), 3.15 (dd, J = 9.7, 4.7 Hz, 1 H, trans), 2.80 (t, J = 4.5 Hz, 1 H, trans), 2.69 (t, J = 4.5 Hz, 1 H, cis), 2.55 (d, J = 12.6 Hz, 1 H, cis), 2.36 (d, J = 9.7 Hz, 1 H, trans), 2.06-1.90 (m, 4 H, cis + trans), 1.87-1.73 (m, 4 H, cis + trans), 1.60-1.54 (m, 2 H, cis + trans), 1.28-1.23 (m, 2 H, cis + trans), 1.25 (d, J = 6.2 Hz, 3 H, trans), 1.22 (d, J = 6.9 Hz, 3 H, cis), 1.20 (d, J = 6.9 Hz, 3 H, cis), 1.18 (t, J = 4.8 Hz, 1 H, trans), 1.15 (d, J = 6.2 Hz, 3 H, trans), 1.11 (dd, J = 9.0, 5.8 Hz, 1 H, cis), 0.87 (dd, J = 10.1, 4.8 Hz, 1 H, trans), 0.46 (t, J = 5.8 Hz, 1 H, cis). ^¹³C NMR (63 MHz, CDCl₃): δ = 170.8 (cis), 170.6 (trans), 137.9 (cis), 137.8 (trans), 128.9 (cis), 128.7 (trans), 128.5 (cis), 128.3 (trans), 127.3 (cis), 127.2 (trans), 68.4 (cis), 68.2 (trans), 66.6 (cis), 65.8(trans), 59.4 (cis), 59.1 (trans), 58.3 (cis), 58.1 (trans), 55.7 (trans), 54.9 (cis), 36.8 (cis), 35.9 (trans), 25.8 (cis), 24.5 (trans), 21.7 (cis), 21.1 (trans), 20.9 (cis), 20.2 (trans), 15.8 (cis), 15.6 (trans). MS (EI, trans isomer): m/z (%) = 303(9) [M⁺], 160 (48), 96 (27), 91 (100). MS (EI, cis isomer): m/z (%) = 303(6) [M⁺], 234 (45), 188 (42), 91 (100). HRMS (ES): m/z calcd for C₁₈H₂₆NO₃ [M + H]⁺: 304.19070; found: 304.19057.
1-Benzyl-4-methyl-2-(2-oxopentyl)-3-pyrrolidinone (6)
Colourless liquid. IR (neat): 3057, 3027, 2955, 1758, 1603 cm^-¹. ^¹H NMR (250 MHz, CDCl₃): δ = 7.36-7.27 (m, 10 H, cis + trans), 3.88 (d, J = 13.0 Hz, 1 H, cis), 3.85 (d, J = 13.0 Hz, 1 H, trans), 3.48 (d, J = 13.7 Hz, 1 H, cis), 3.46 (d, J = 13.0 Hz, 1 H, trans), 3.40 (t, J = 8.3 Hz, 1 H, trans), 3.29 (t, J = 5.0 Hz, 1 H, cis), 3.01 (dd, J = 11.2, 9.0 Hz, 1 H, trans), 2.85 (dd, J = 12.6, 7.2 Hz, 1 H, cis), 2.73 (dd, J = 12.6, 7.2 Hz, 1 H, cis), 2.68 (dd, J = 11.2, 8.3 Hz, 2 H, cis), 2.67-2.60 (m, 2 H, cis + trans), 2.63 (dd, J = 10.0, 5.0 Hz, 2 H, trans), 2.27-2.20 (m, 4 H, cis + trans), 2.08 (dd, J = 11.2, 9.0 Hz, 1 H, trans), 1.60-1.54 (m, 4 H, cis + trans), 1.21 (d, J = 7.6 Hz, 3 H, cis), 1.14 (d, J = 7.2 Hz, 3 H, trans), 1.07 (t, J = 7.6 Hz, 3 H, cis), 1.06 (t, J = 7.6 Hz, 3 H, trans). ^¹³C NMR (63 MHz, CDCl₃): δ = 217.7 (cis), 217.5 (trans), 208.1 (cis), 207.8 (trans), 138.2 (cis), 138.0 (trans), 128.9 (trans), 128.7 (cis), 128.4 (cis), 128.2 (trans), 127.5 (trans), 127.3 (cis), 66.4 (trans), 66.0 (cis), 59.4 (trans), 58.9 (cis), 57.9 (trans), 56.7 (cis), 45.2 (cis), 43.1 (trans), 41.9 (cis + trans), 36.2 (cis), 35.3 (trans), 18.0 (cis), 17.1 (cis), 17.0 (trans), 16.0 (cis), 13.7 (trans), 11.9 (trans). MS (EI, trans isomer): m/z (%) = 273 (5) [M⁺], 86 (40), 84 (61), 55 (55), 51 (35), 49 (100), 44 (49), 40 (90). MS (EI, cis isomer):
m/z (%) = 273 (4) [M⁺], 91 (100), 86 (41). HRMS (ES): m/z calcd for C₁₇H₂₄NO₂ [M + H]⁺: 274.18020; found: 274.18082.
(1 S ,2 S )-3-Benzyl-2-[2-(1-hydroxy-2-methylcyclopropyl)-ethyl]-3-azabicyclo[3.1.0]hexan-1-ol (13)
[Insepable mixture of undetermined cis and trans diastereomers (ratio 60:40: major a and minor b) on the side chain.]Colorless liquid. IR (neat): 3030, 2929, 2797, 1603 cm^-¹. ^¹H NMR (360 MHz, CDCl₃): δ = 7.34-7.26 (m, 10 H, a + b), 4.14 (d, J = 14.4 Hz, 1 H, b), 4.08 (d, J = 14.4 Hz, 1 H, b), 3.76 (d, J = 13.7 Hz, 1 H, a), 3.71 (d, J = 13.7 Hz, 1 H, a), 3.23 (dd, J = 12.6, 5.8 Hz, 1 H, b), 3.06 (dd, J = 9.7, 4.3 Hz, 1 H, a), 2.92 (t, J = 4.7 Hz, 1 H, a), 2.65 (t, J = 4.2 Hz, 1 H, b), 2.53 (d, J = 12.6 Hz, 1 H, b), 2.44 (d, J = 9.7 Hz, 1 H, a), 2.21-2.17 (m, 4 H, a + b), 2.06-1.97 (m, 4 H, a + b), 1.63-1.54 (m, 2 H, a + b), 1.44-1.39 (m, 2 H, a + b), 1.40 (t, J = 5.1 Hz, 1 H, a), 1.30-1.24 (m, 2 H, a + b), 1.26 (t, J = 5.8 Hz, 1 H, b), 1.18-1.08 (m, 2 H, a + b), 1.16 (d, J = 6.2 Hz, 3 H, a), 1.07 (d, J = 6.2 Hz, 3 H, b), 0.97-0.87 (m, 4 H, a + b), 0.81 (dd, J = 9.4, 5.1 Hz, 1 H, a), 0.07 (dd, J = 10.2, 5.8 Hz, 1 H, b). ^¹³C NMR (63 MHz, CDCl₃): δ = 139.7 (b), 137.9 (a), 129.6 (b), 128,7 (a), 128.5 (b), 128.3 (a), 128.2 (b), 127.5 (a), 70.2 (b), 70.1 (a), 65.7 (a), 64.6 (b), 57.8 (b), 57.7 (a), 55.8 (a), 55.7 (b), 54.1 (a), 53.4 (b), 37.3 (a), 31.1 (b), 24.6 (a), 24.5 (b), 22.7 (a), 22.1 (b), 20.2 (a), 18.4 (b), 17.4 (a), 16.5 (b), 14.4 (a), 13.8 (b), 12.4 (b), 11.4 (a). MS (EI, isomer a): m/z (%) = 287 (5)[M⁺], 218 (18), 200(20), 188(47), 91(100). MS (EI, isomer b): m/z (%) = 287 (6) [M⁺], 218 (17), 200(26), 188 (29), 91(100). HRMS (ES): m/z calcd for C₁₈H₂₆NO₂ [M + H]⁺: 288.19580; found: 288.19622.
(1 R ,2 S ) - 3-Benzyl-2-[2-(1-hydroxy-2-methylcyclo-propyl)ethyl]-3-azabicyclo[3.1.0]hexan-1-ol (14) [Inseparable mixture of undetermined cis and trans diastereomers (ratio 64:36: major a and minor b) on the
side chain.]Colourless liquid. IR (neat): 3036, 2929, 2791, 1602 cm^-¹. ^¹H NMR (360 MHz, CDCl₃): δ = 7.34-7.25 (m, 10 H, a + b), 3.84 (d, J = 13.3 Hz, 1 H, a), 3.83 (d, J = 13.3 Hz, 1 H, b), 3.64 (d, J = 13.3 Hz, 1 H, a), 3.63 (d, J = 13.3 Hz, 1 H, b), 3.17 (dd, J = 10.1, 4.7 Hz, 1 H, b), 3.02 (t, J = 4.2 Hz, 1 H, a), 2.97 (t, J = 4.2 Hz, 1 H, b), 2.34 (d, J = 9.4 Hz, 1 H, a), 2.31 (d, J = 10.1 Hz, 1 H, b), 2.29 (dd, J = 9.4, 4.0 Hz, 1 H, a), 2.01-1.92 (m, 4 H, a + b), 1.83-1.73 (m, 4 H, a + b), 1.59-1.54 (m, 2 H, a + b), 1.47-1.45 (m, 2 H, a + b), 1.29 (t, J = 6.7 Hz, 1 H, a), 1.28-1.25 (m, 2 H, a + b), 1.17 (dd, J = 9.0, 5.4 Hz, 1 H, b), 1.06 (d, J = 6.7 Hz, 3 H, a), 1.04 (d, J = 6.7 Hz, 3 H, b), 0.93 (dd, J = 9.0, 6.7 Hz, 1 H, a), 0.86-0.81 (m, 2 H, a + b), 0.76-0.73 (m, 4 H, a + b), 0.02 (t, J = 10.2 Hz, 1 H, b). ^¹³C NMR (63 MHz, CDCl₃): δ = 139.2 (b), 137.6 (a), 129.4 (a + b), 128,7 (b), 128.6 (a), 128.3 (b), 127.1 (a), 67.1 (b), 66.3 (a), 63.4 (a), 63.2 (b), 58.7 (a), 58.4 (b), 57.8 (a), 57.4 (b), 54.7 (b), 54.2 (a), 30.8 (a), 30.4 (b), 24.6 (a), 24.4 (b), 21.6 (a), 20.4 (b), 20.2 (a), 20.0 (b), 19.6 (a), 19.1 (b), 15.0 (a), 14.9 (b), 14.6 (b), 14.3 (a). MS (EI, isomer a): m/z (%) = 287 (9)[M⁺], 218 (21), 200 (23), 188 (22), 91 (100). MS (EI, isomer b): m/z (%) = 287(6) [M⁺], 218 (28), 200 (19), 188 (33), 91 (100). HRMS (ES): m/z calcd for C₁₈H₂₆NO₂ [M + H]⁺: 288.19580; found: 288.19653.