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Synlett 2008(5): 735-738  
DOI: 10.1055/s-2008-1042808
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© Georg Thieme Verlag Stuttgart · New York

Regio- and Stereoselective Direct Cross-Coupling of Aromatic Imines with Allenic Alcohols

Martin McLaughlin, Heidi L. Shimp, Raul Navarro, Glenn C. Micalizio*
Department of Chemistry, Yale University, New Haven, CT 06520, USA
Fax: +1(203)4326144; e-Mail: glenn.micalizio@yale.edu;
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Publication History

Received 13 November 2007
Publication Date:
10 March 2008 (online)

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Abstract

We describe a titanium-mediated reaction for the convergent coupling of allenic alcohols with aromatic imines. Overall, the bond formation occurs at the central carbon of the allene, proceeds with net allylic transposition, and provides substituted 1,3-dienes bearing allylic amine functionality in a regio- and stereoselective fashion.

Key words

imines - allenes - cross-coupling - metallacycles - titanium

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Experimental Procedure for the Preparation of 7
A solution of imine 5 (0.075 g, 0.333 mmol) in Et2O (2.2 mL) was cooled to -60 °C, and ClTi(Oi-Pr)3 (1.0 M solution in hexanes, 0.416 mmol) was added dropwise with a gas-tight syringe. The reaction was then cooled to -70 °C and
c-C5H9MgCl (2.02 M solution in Et2O, 0.832 mmol) was added dropwise with a gas-tight syringe. During the addition the solution turned light brown in color. The reaction was then slowly warmed to -45 °C over 30 min and stirred at
-45 °C for an additional 90 min. Next, a solution of allenyl alkoxide 6, generated from the deprotonation of the corresponding alcohol (0.093 g, 1.33 mmol) with n-BuLi (2.5 M in hexanes, 1.33 mmol), in Et2O (2 mL) at
-78 °C warming to 0 °C over 30 min, was added via Teflon cannula. The reaction was then warmed to 0 °C over 60 min and stirred at 0 °C 6 h. The reaction was then quenched at 0 °C with 5 mL of sat. aq NH4Cl and the resulting biphasic mixture was rapidly stirred overnight at r.t. The reaction mixture was further diluted with sat. NaHCO3, and extracted with EtOAc. The combined organic phases were washed with brine, dried over MgSO4, and concentrated in vacuo. The crude material was purified by column chromatography on silica gel (4% → 8% EtOAc-hexanes) to yield amine 7 as a colorless oil (53 mg, 57%). 1H NMR (500 MHz, CDCl3):
δ = 7.42-7.39 (m, 2 H), 7.34-7.30 (m, 2 H), 7.27-7.23 (m, 3 H), 6.88-6.85 (m, 2 H), 6.32 (dd, J = 17.7, 11.3 Hz, 1 H), 6.39 (s, 1 H), 5.31 (s, 1 H), 5.28 (d, J = 17.9 Hz, 1 H), 5.01 (d, J = 11.4 Hz, 1 H), 4.52 (s, 1 H), 3.80 (s, 3 H), 3.68 (dd, J = 21.8, 12.9 Hz, 2 H), 1.61 (br s, 1 H). 13C NMR (126 MHz, CDCl3): δ = 158.9, 147.6, 142.5, 137.1, 132.9, 129.6, 128.5, 127.9, 127.3, 115.9, 114.7, 114.0, 63.2, 55.5, 51.4. IR (thin film, NaCl): 3004, 2935, 2833, 1512, 1246, 1611 cm- 1. LRMS (EI, H): m/z calcd for C19H22NO: 280.2 [M + H]; found: 280.1 [M + H]+.

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Experimental details for this reaction can be obtained on request from the author.