Enantioselective Intramolecular Büchner Reaction of α-Diazoketones

Abstract

Enantioselectivities of up to 95% ee have been achieved in the intramolecular Büchner reaction catalysed by copper bis(oxazoline) complexes, the highest asymmetric inductions reported to date for this transformation. Significantly, use of a catalyst derived from a bis(oxazoline) ligand resulted in high enantioselectivities across several substrates, indicating the possibility of developing a catalyst with general applicability.

intramolecular Büchner reaction - α-diazoketones - carbenes - copper bis(oxazoline) catalysts - asymmetric synthesis

References and Notes

1 Kennedy M. McKervey MA. Maguire AR. Roos GHP. J. Chem. Soc., Chem. Commun.  1990,  361 

2 Doyle MP. McKervey MA. Ye T. Modern Catalytic Methods for Organic Synthesis with Diazo Compounds   Wiley; New York: 1998. 

3 McCarthy N. McKervey MA. Ye T. Tetrahedron Lett.  1992,  33:  5983 

4 Doyle MP. Ene D. Forbes GDC. Pillow TH. Chem. Commun.  1999,  1691 

5

It is generally accepted that copper(I) rather than copper(II) is the active form of copper in diazo decomposition reactions and although the initial copper species in CuSbF₆-based catalyst has an oxidation state of +2, this is reduced during the reaction. See ref. 2.

6 Hannemann K. Angew. Chem. Int. Ed.  1998,  27:  284 

7

General Experimental Procedure
3,8a-Dihydro-3,3,8a-trimethylazulen-1-(2 H )-one (7)
Diazoketone 6 (100 mg, 0.46 mmol) in CH₂Cl₂ (75 mL) was added dropwise over 1 h to a refluxing solution of [Cu(MeCN)₄]PF₆ (8.6 mg, 0.023 mmol) and ligand 2 (2.2 mg, 0.030 mmol) in CH₂Cl₂ (75 mL). The progress of the reaction was monitored by TLC and was found to be complete upon diazoketone addition. Evaporation of the solvent at reduced pressure gave the crude product as a yellow oil. A ¹H NMR spectrum was recorded to determine the efficiency of the cyclisation (99%; percent of azulenone 7 relative to aromatic byproducts). Purification by flash chromatography, using EtOAc-hexane (5%) as eluant, gave the azulenone 7 (84 mg, 97%) as a colourless oil.
IR (film): ν_max = 1748 s (CO), 1716 s (CO) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 6.21-6.44 [2 H, m, C(4)H, C(5)H, C(6)H], 6.10 [1 H, overlapping dd appears as t, J = 7.6, 7.6 Hz, C(7)H], 4.15 [1 H, d, J = 7.9 Hz, C(8)H], 2.28 [1 H, B of ABq, J _AB = 17.3 Hz, one of C(2)H₂], 2.20 [1 H, A of ABq, J _AB = 17.3 Hz, one of C(2)H₂], 1.31, 1.14 [2 × 3 H, 2 × s, C(3)(CH₃)₂], 0.75 [3 H, s, C(8a)CH₃]. ¹³C NMR (60 MHz, CDCl₃): δ = 218.4 [C(1)], 127.2, 126.9, 125.3, 119.7 [C(4)H, C(5)H, C(6)H, C(7)H], 101.6 [C(3a)], 89.1 br [C(8)H], 50.2 [C(2)H₂], 41.3 [C(3)], 38.6 [C(8a)], 28.8, 28.7 [C(CH₃) ₂ ], 11.6 [C(8a)CH₃]. HRMS (EI): m/z calcd for C₁₃H₁₆O: 188.1201; found: 188.1187; 76% ee [by ¹H NMR analysis using (+)-Eu(hfc)₃]; [α]_D ²⁰ -35.2 (c 1.0, CHCl₃).

8 Maguire AR. Buckley NR. O’Leary P. Ferguson G. Chem. Commun.  1998,  2696 

9 Maguire AR. Buckley NR. O’Leary P. Ferguson G. J. Chem. Soc., Perkin Trans. 1  1996,  4077