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DOI: 10.1055/s-0030-1259039
Regioselective Synthesis of Optically Active Trifluoromethyl Group Substituted Allylic Amines by Palladium-Catalyzed Allylic Amination
Publication History
Publication Date:
10 November 2010 (online)

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
- Supporting Information for this article is available online:
- Supporting Information (PDF)
- 1a
Tsuji J. Palladium Reagents and Catalysts: New Perspectives for the 21st Century John Wiley and Sons; Chichester: 2004.Reference Ris Wihthout Link - 1b
Tsuji J. Transition Metal Reagents and Catalysts: Innovations in Organic Synthesis Wiley and Sons; Chichester: 2000.Reference Ris Wihthout Link - 1c
Trost BM.Lee CB. In Catalytic Asymmetric Synthesis IIOjima I. Wiley-VCH; Weinheim: 2000.Reference Ris Wihthout Link - 1d
Pfaltz A.Lautens M. In Comprehensive Asymmetric Catalysis I-IIIJacobsen EN.Pfaltz A.Yamamoto H. Springer; Berlin: 1999.Reference Ris Wihthout Link - 1e
Hayashi T. In Catalytic Asymmetric SynthesisOjima I. Wiley-VCH; Weinheim: 1993.Reference Ris Wihthout Link - 2a
Jørgensen KA. In Modern Amination MethodsRicci A. Wiley-VCH; Weinheim: 2000. Chap. 1. p.1Reference Ris Wihthout Link - 2b
Johannsen M.Jørgensen KA. Chem. Rev. 1998, 98: 1689Reference Ris Wihthout Link - Selected examples of transition-metal-catalyzed allylic aminations of allylic esters: for [Pd]
- 3a
Dubovyk I.Watson IDG.Yudin AK. J. Am. Chem. Soc. 2007, 129: 14172Reference Ris Wihthout Link - 3b
Johns AM.Liu Z.Hartwig JF. Angew. Chem. Int. Ed. 2007, 46: 7259Reference Ris Wihthout Link - 3c
Faller JW.Wilt JC. Org. Lett. 2005, 7: 633 ; and references thereinReference Ris Wihthout Link - For [Ir]:
- 3d
Takeuchi R.Ue N.Tanabe K.Yamashita K.Shiga N. J. Am. Chem. Soc. 2001, 123: 9525Reference Ris Wihthout Link - 3e
Ohmura T.Hartwig JF. J. Am. Chem. Soc. 2002, 124: 15164Reference Ris Wihthout Link - 3f
Leitner A.Shekhar S.Pouy MJ.Hartwig JF. J. Am. Chem. Soc. 2005, 127: 15506Reference Ris Wihthout Link - 3g
Polet D.Alexakis A.Tissot-Croset K.Corminboeuf C.Ditrich K. Chem. Eur. J. 2006, 12: 3596Reference Ris Wihthout Link - 3h
Weihofen R.Tverskoy O.Helmchen G. Angew. Chem. Int. Ed. 2006, 45: 5546 ; and references thereinReference Ris Wihthout Link - For [Rh]:
- 3i
Evans PA.Robinson JE.Nelson JD. J. Am. Chem. Soc. 1999, 121: 6761Reference Ris Wihthout Link - 3j
Evans PA.Robinson JE.Nelson JD. J. Am. Chem. Soc. 1999, 121: 12214Reference Ris Wihthout Link - For [Ru]:
- 3k
Morisaki Y.Kondo T.Mitsudo T. Organometallics 1999, 18: 4742Reference Ris Wihthout Link - 3l
Matsushima Y.Onitsuka K.Kondo T.Mitsudo T.Takahashi S. J. Am. Chem. Soc. 2001, 123: 10405Reference Ris Wihthout Link - 3m
Matsushima Y.Onitsuka K.Takahashi S. Organometallics 2004, 23: 3763Reference Ris Wihthout Link - 3n
Kawatsura M.Ata F.Hirakawa T.Hayase S.Itoh T. Tetrahedron Lett. 2008, 49: 4873 ; and references cited thereinReference Ris Wihthout Link - Examples of allylic substitutions of fluorinated allyl substrates:
- 4a
Hanzawa Y.Ishizawa S.Kobayashi Y. Chem. Pharm. Bull. 1988, 36: 4209Reference Ris Wihthout Link - 4b
Hanzawa Y.Ishizawa S.Ito H.Kobayashi Y.Taguchi T. J. Chem. Soc., Chem. Commun. 1990, 394Reference Ris Wihthout Link - 4c
Fish PV.Reddy SP.Lee CH.Johnson WS. Tetrahedron Lett. 1992, 33: 8001Reference Ris Wihthout Link - 4d
Konno T.Ishihara T.Yamanaka H. Tetrahedron Lett. 2000, 41: 8467Reference Ris Wihthout Link - 4e
Okano T.Matsubara H.Kusukawa T.Fujita M. J. Organomet. Chem. 2003, 676: 43Reference Ris Wihthout Link - 4f
Konno T.Takehana T.Ishihara T.Yamanaka H. Org. Biomol. Chem. 2004, 2: 93Reference Ris Wihthout Link - 4g
Konno T.Takehana T.Mishima M.Ishihara T. J. Org. Chem. 2006, 71: 3545Reference Ris Wihthout Link - 4h
Kawatsura M.Wada S.Hayase S.Itoh T. Synlett 2006, 2483Reference Ris Wihthout Link - 5
Konno T.Nagata K.Ishihara T.Yamanaka H. J. Org. Chem. 2002, 67: 1768 - 6
Kawatsura M.Hirakawa T.Tanaka T.Ikeda D.Hayase S.Itoh T. Tetrahedron Lett. 2008, 49: 2450 - Examples of net retention mechanism in the palladium-catalyzed allylic substitutions:
- 7a
Hayashi T.Hagihara T.Konishi M.Kumada M. J. Am. Chem. Soc. 1983, 105: 7767Reference Ris Wihthout Link - 7b
Hayashi T.Yamamoto A.Hagihara T. J. Org. Chem. 1986, 51: 723Reference Ris Wihthout Link - 7c
Trost BM.Toste FD. J. Am. Chem. Soc. 1999, 121: 4545Reference Ris Wihthout Link - Selected examples of kinetic resolution in the palladium-catalyzed allylic substitutions of disubstituted symmetrical or monosubstituted allylic esters:
- 12a
Cook GR. Curr. Org. Chem. 2000, 4: 869Reference Ris Wihthout Link - 12b
Robinson DEJE.Bull SD. Tetrahedron: Asymmetry 2003, 14: 1407Reference Ris Wihthout Link - 12c
Longmire JM.Wang B.Zhang X. Tetrahedron Lett. 2000, 41: 5435Reference Ris Wihthout Link - 12d
Reetz MT.Sostmann S. J. Organomet. Chem. 2000, 603: 105Reference Ris Wihthout Link - 12e
Gilbertson SR.Lan P. Org. Lett. 2001, 3: 2237Reference Ris Wihthout Link - 12f
Cook GR.Sankaranarayanan S. Org. Lett. 2001, 3: 3531Reference Ris Wihthout Link - 12g
Lüssem BJ.Gais H.-J. J. Org. Chem. 2004, 69: 4041Reference Ris Wihthout Link - 12h
Castillo AB.Favier I.Teuma E.Castillón S.Godard C.Aghmiz A.Claver C.Gómez M. Chem. Commun. 2008, 6197Reference Ris Wihthout Link - 12i
Hou XL.Zheng BH. Org. Lett. 2009, 11: 1789 ; and references cited thereinReference Ris Wihthout Link - Examples of kinetic resolution in the palladium-catalyzed allylic substitutions of 1,3-disubstituted unsymmetrical allylic esters:
- 13a
Hayashi T.Yamamoto A.Ito Y.
J. Chem. Soc., Chem. Commun. 1986, 1090Reference Ris Wihthout Link - 13b
Faller JW.Wilt JC. Tetrahedron Lett. 2004, 45: 7613Reference Ris Wihthout Link - 15
Kagan HB.Fiaud JC. Top. Stereochem. 1988, 18: 249
References and Notes
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.
9We 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%.
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.
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.
14Calculated by eeP and eeS. S = ln[(1 - c)(1 + eeP)]/ln[(1 - c) (1 - eeP)]. c = eeS/(eeS + eeP).