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Synlett 2010(19): 2887-2890  
DOI: 10.1055/s-0030-1259039
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Synthesis of Optically Active Trifluoromethyl Group Substituted Allylic Amines by Palladium-Catalyzed Allylic Amination

Takuya Hirakawa, Kazunori Ikeda, Hiroshi Ogasa, Motoi Kawatsura*, Toshiyuki Itoh*
Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Koyama, Tottori 680-8552, Japan
Fax: +81(857)315179; e-Mail: kawatsur@chem.tottori-u.ac.jp; e-Mail: titoh@chem.tottori-u.ac.jp;
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Publication History

Received 15 September 2010
Publication Date:
10 November 2010 (online)

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Abstract

We succeeded in the regioselective synthesis of chiral trifluoromethyl group substituted allylic amines from chiral allyl acetate using two types of palladium catalysts. Furthermore, we found that the kinetic resolution had occurred during the isomerization step from the γ-type product to the α-type product by the [Pd(C3H5)(cod)]BF4/(S)-BINAP catalyst.

Key words

palladium catalyst - allylic amination - trifluoromethyl group - chiral allylic amine - kinetic resolution

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8

We observed the racemization of allylic amines took place by palladium catalysts. For example, the ee of (R)-4a decreased from 88% to 80% by Pd(OAc)2/DPPE at 60 ˚C for 12 h, and the ee of (S)-3a also decreased from 98% to 13% by [Pd(C3H5)(cod)]BF4/(S)-BINAP at 100 ˚C for 12 h.

9

We also confirmed the reaction with 10 mol% of [Pd(C3H5)(cod)]BF4/BIPHEP [2,2′-bis(diphenyl-phosphino)-1,1′-biphenyl] gave an α-product with 96% regioselectivity at 60 ˚C, but the ee decreased to 66%.

10

Typical Procedure for the [Pd(C 3 H 5 )(cod)]BF 4 /( S )-BINAP-Catalyzed Allylic Amination of ( S )-1 with 2a To a solution of [Pd(C3H5)(cod)]BF4 (7.0 mg, 0.021 mmol), (S)-BINAP (12.8 mg, 0.021 mmol), (S)-1,1,1-trifluoro-4-phenylbut-3-en-2-yl acetate [(S)-1, 50 mg, 0.21 mmol] in dioxane (1.0 mL) was added morpholine (2a) and stirred at r.t. for 5 min and 40 ˚C for 12 h. The reaction mixture was quenched with brine and H2O (1 mL), then extracted with EtOAc (3 × 2 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The NMR yield (95%, trioxane as an internal standard) and ratio of 3a and 4a was determined by ¹H NMR of the crude materials.
Analytical Data of 3a
[α]D ²6 +69.2 [c 1.37, CHCl3; 99% ee (S)]. The enantiomeric purity was determined to be 99% ee by HPLC analysis with a Daicel CHIRALPAK AD-H [hexane-2-PrOH (99:1), flow: 1.0 mL/min, 254 nm, 35 ˚C, t major = 11.2 min, t minor = 13.0 min]. ¹H NMR (500 MHz, CDCl3): δ = 2.71-2.80 (m, 4 H), 3.60 (quin, J = 8.2 Hz, 1 H), 3.72 (t, J = 4.6 Hz, 4 H), 6.18 (dd, J = 8.2, 16.0 Hz, 1 H), 6.72 (d, J = 16.0 Hz, 1 H), 7.28-7.42 (m, 5 H). ¹³C NMR (125 MHz, CDCl3): δ = 50.4, 67.2, 68.6 (q, J CF = 27.5 Hz), 118.5, 125.7 (q, J CF = 285.0 Hz), 126.7, 128.5, 128.7, 135.7, 137.5. ¹9F NMR (470 MHz, CDCl3): δ = 92.0 (d, J = 8.2 Hz). HRMS (EI): m/z calcd for C14H16F3NO: 271.1184; found: 271.1195.

11

The absolute configuration of (S)-3a and (R)-4a were determined by the comparison of the X-ray crystallographic analysis of the products from the reaction of (S)-4-(4-chlorophenyl)-1,1,1-trifluorobut-3-en-2-yl acetate with 1-phenylpiperazine. See details in the Supporting Information.

14

Calculated by eeP and eeS. S = ln[(1 - c)(1 + eeP)]/ln[(1 - c) (1 - eeP)]. c = eeS/(eeS + eeP).