A New Class of Chiral Lewis Basic Metal-Free Catalysts for Stereoselective Allylations of Aldehydes

Abstract

A new class of amine N-oxides derived from trans-2,5-diphenylpyrrolidine were synthesized in enantiomerically pure form and tested as metal-free catalysts in the reaction of aldehydes with allyl(trichloro)silane to afford homoallylic alcohols. The products were obtained in fair to good yields and up to 85% ee. The behavior of structurally different catalysts and the influence of a coordinating unit present in the organocatalyst on controlling the stereochemical efficiency of the reaction were also investigated. Noteworthy a catalyst capable of promoting the allylation of aliphatic aldehydes with an almost unprecedent and unusually high enantioselectivity, up to 85%, was identified.

Key words

N-oxides - allyltrichlorosilane - homoallylic alcohol - enantioselective catalysis - organocatalysis

References and Notes

• 1 Orito Y. Nakajima M. Synthesis  2006,  1391 
• 2 Benaglia M. Guizzetti S. Pignataro L. Coord. Chem. Rev.  2008, , DOI: 10.1016/j.ccr.2007.10.009
• 3 Chuit C. Corriu RJP. Reye C. Young JC. Chem. Rev.  1993,  93:  1371 
• 4 See ref. 1, 2, and: Rendler S. Oestreich M. Synthesis  2005,  1727 
• 5a Denmark SE. Fu J. Coe DM. Su X. Pratt NE. Griedel BD. J. Org. Chem.  2006,  71:  1513 ; and references cited therein
• 5b Denmark SE. Fu J. Chem. Rev.  2003,  103:  2763 
• 6a Nakajima M. Kotani S. Ishizuka T. Hashimoto S. Tetrahedron Lett.  2005,  46:  157 
• 6b Kotani S. Hashimoto S. Nakajima M. Tetrahedron  2007,  63:  3122 
• 7 Malkov AV. Kočovsk P. Eur. J. Org. Chem.  2007,  29 
• 8 Malkov AV. Dufkovà A. Farrugia L. Kocovsky P. Angew. Chem. Int. Ed.  2003,  42:  3674 
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• 18 Enantioselectivities reported for product 10f were very often lower than 50%. For the only notable exception, see: Chai Q. Song C. Sun Z. Ma Y. Ma C. Dai Y. Andrus MB. Tetrahedron Lett.  2006,  47:  8611 
• 19 See: Denmark SE. Fu J. Lawler MJ. J. Org. Chem.  2006,  71:  1523 ; and references cited therein

13

Reaction of (1 R ,4 R )-1,4-Bis-(methansulfonyl)-1,4-diphenylbutan with Ethylene Diamine and Formylation Reaction
A solution of ethylene diamine (8.45 g. 8.45 mmol) in CH₂Cl₂ (3 mL) was added under dry atmosphere at 0 °C to (1R,4R)-1,4-bis-(methansulfonyl)-1,4-diphenylbutan (0.587 g, 1.47 mmol). The reaction mixture was allowed to react at 0 °C for 16 h, then ethylene diamine and the solvent were evaporated under reduced pressure. The crude product was purified by a short column on silica gel (CH₂Cl₂-MeOH = 8:2 as eluent mixture). A white waxy solid was obtained and used as such in the step (>98% yield). To a solution of the amine (0.428 g, 1.6 mmol) in formic acid (2.9 g, 63.4 mmol) cooled to 0 °C, Ac₂O (1.15 g, 11.2 mmol) was added dropwise. The reaction mixture was allowed to stir at r.t. for 20 h, then it was quenched with H₂O and solid K₂CO₃ to make the solution alkaline. The aqueous phase was extracted 3 times with CH₂Cl₂, the organic phase was then dried over Na₂SO₄ and evaporated under reduced pressure. The purification by flash chromatography (CH₂Cl₂-EtOAc = 7:3 as eluent mixture) afforded the diol as colorless oil (53% yield). ¹H NMR (300 MHz, CDCl₃): δ = 8.01 (s, 1 H), 7.39-7.21 (m, 10 H), 5.68 (br s, 1 H), 3.07 (m, 2 H), 2.57 (m, 2 H), 2.46 (m, 2 H), 1.96 (m, 2 H). MS (ESI⁺): m/z = 317.5 [M + Na]⁺. [α]²³ -131.0 (c 0.41, CHCl₃). IR (CH₂Cl₂): ν_C=O = 1685.5 cm^-1.

14

N-Oxidation To a solution of the N-formyl pyrrolidine (0.11 g, 0.35 mmol) in CH₂Cl₂ (7 mL) at -78 °C under nitrogen atmosphere K₂CO₃ (0.10 g, 0.76 mmol) and MCPBA 70% (0.092 g, 037 mmol) were added; the reaction mixture was stirred at -78 °C, followed by TLC and stopped after 6 h by filtering the mixture onto Celite cake. The organic phase was washed 3 times with K₂CO₃ sat. soln, dried over Na₂SO₄ and evaporated under reduced pressure. The purification by flash chromatography (CH₂Cl₂-MeOH = 95:5 as eluent mixture) afforded catalyst 5 as white solid (73% yield); mp 139-141 °C; [α]²³ -229.3 (c 0.48 in CHCl₃). IR: ν_C=O = 1669.09 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 8.65 (br s, 1 H), 7.91 (s, 1 H), 7.65 (m, 4 H), 7.50 (m, 5 H), 7.40 (m, 3 H), 5.00 (dd, 1 H), 4.55 (dd, 1 H), 3.45 (m, 1 H), 3.15 (m, 1 H), 3.00 (m, 1 H), 2.85 (m, 1 H), 2.65 (m, 1 H), 2.5 (m, 1 H), 2.25 (m, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 160.8, 137.1, 132.4, 131.7, 129.8, 129.7, 129.5, 129.4, 128.2, 86.1, 76.8, 59.0, 34.2, 29.6, 28.2. MS (ESI⁺): m/z 333.5 [M + Na]⁺. Anal. Calcd for C₁₉H₂₂N₂O₂: C, 72.52; H, 7.14; N, 9.03. Found: C, 72.45; H, 7.18; N, 9.08.

15

Allylation Reaction - Typical Procedure To a stirred solution of catalyst (0.03 mmol) in MeCN (2 mL) kept under nitrogen, an aldehyde (0.3 mmol) and DIPEA (0.154 mL, 0.9 mmol) were added in this order. The mixture was then cooled to 0 °C and allyl(trichloro)silane (0.054 mL, 0.36 mmol) was added dropwise by means of a syringe. After 48 h stirring at 0 °C the reaction was quenched by the addition of a saturated aqueous solution of NaHCO₃ (1 mL). The mixture was allowed to warm up to r.t. and H₂O (2 mL) and EtOAc (5 mL) were added. The organic phase was separated and the aqueous phase was extracted 3 times with EtOAc. The combined organic phases were dried over Na₂SO₄, filtered, and concentrated under vacuum at r.t. to afford the crude products. These were purified by flash chromatography with different hexanes-ethyl acetate mixture as eluents. Yields and ee for each reaction are indicated in Tables [1] and [2] . The assignment of the R absolute configuration to the predominant isomer formed in each reaction rests on comparison of sign of optical rotation with those reported in the literature, or on the reasonable assumption that the absolute configuration of the alcohols obtained by the reaction with a given catalyst is independent on the structure of the aldehyde.

16

For a discussion on the proposed transition states for these reactions, see ref. 2, 5, and 7.

17

The reaction performed in other solvents such as toluene, hexane, or THF afforded the product with lower stereoselectivity.