Journal of the American Chemical Society
Article
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(+)-137.3°). 1H, 13C{1H}, and 19F NMR spectra and H−15N HMBC
experiments were collected either on a Bruker DRX-400 spectrometer,
Bruker Avance III 600 spectrometer, or an Agilent MR 400
spectrometer. 15N NMR chemical shifts are referenced to a
nitromethane external standard. [α]D values were measured on a
ATAGO AP-300 polarimeter at 23 °C.
AUTHOR INFORMATION
Corresponding Author
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Present Address
†Department of Chemistry, University of Chicago, 5735 S. Ellis
Ave., Chicago, IL 60637.
19F NMR Spectroscopic Determination of Enantiomeric
Excess. The cyclic amine, (+)-(S)-α-methoxy-α-(trifluoromethyl)-
phenylacetyl chloride (1.2 equiv), and NEt3 (5.0 equiv) were allowed
to react in benzene. Evaporation of volatile materials after 1 h,
followed by pentane extraction (3 × 4 mL) gives a colorless oil.
Integration of 19F NMR (60 °C, CDCl3) signals for racemic- and
optically-enriched samples provided data to determine % ee.
HPLC Analysis of Enantioselectivity. The % ee was determined
by HPLC analysis (flow rate =1.0 mL/min, λ = 254 nm) using Regis
(S,S)-Whelk O1 column (column dimensions = 25 cm × 4.6 mm i.d.,
Spherical Kromasil Silica, particle size = 5 μm, 100 Å). The chiral
pyrrolidines and piperidines were converted to benzoyl derivative prior
to HPLC analysis. Pure samples of cyclic imines were used to
determine their enantiomeric excesses by HPLC.
4-Allyl-2-methyl-4-(4-bromophenyl)pyrrolidine (4b). {S-1}-
Zr(NMe2)2 (0.120 g, 0.196 mmol), benzene (30 mL), and 4a (0.549 g,
1.96 mmol) were stirred at room temperature for 4 h. Vacuum
distillation of the reaction mixture provided the product 4b (bp 120−
125 °C, 0.1 mmHg) in excellent yield (0.398 g, 1.42 mmol, 94.3%).
The isolated 4b was a mixture of cis and trans diastereomers (cis:trans
= 4:1; ee (cis) = 97%, ee (trans) = 95%) determined by 19F NMR
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This research was supported by the U.S. Department of Energy,
Office of Basic Energy Sciences, Division of Chemical Sciences,
Geosciences, and Biosciences through the Ames Laboratory
(contract no. DE-AC02-07CH11358). Prof. M. Jeffries-EL is
thanked for generous access to an HPLC.
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spectroscopy. H NMR (chloroform-d1, 400 MHz): δ 7.43−7.40 (m,
C6H4Br), 7.10−7.02 (m, C6H4Br), 5.49−5.39 (m, CHCH2), 4.97−
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CHMeNH), 1.17 (d, 3JHH = 6.0 Hz, CHMeNH). 13C{1H} NMR (100
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(CHCH2), 134.60 (CHCH2), 131.38 (C6H4Br), 131.29
(C6H4Br), 128.89 (C6H4Br), 128.88 (C6H4Br), 119.93 (C6H4Br),
119.90 (C6H4Br), 118.03 (CHCH2), 117.94 (CHCH2), 57.94
(CH2NH), 57.15 (CH2NH), 54.26 (CHMeNH), 53.33 (CHMeNH),
51.90 (C(C6H4Br), 51.84 C(C6H4Br), 47.24 (CH2CHCH2), 46.0
(CH2CHCH2), 45.63 (CH2CHMe), 45.38 (CH2CHMe), 22.40
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−346.2, −347.5 MS (ESI) exact mass calcd for C14H18BrN: m/z
23
280.0695 ([M+ + H+]); found: 280.0700. (Δ −1.65 ppm). [α]D
−34.3° (C6H6).
=
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95.1% yield, 87% ee). H NMR (chloroform-d1, 400 MHz): δ 7.35−
7.30 (m, 2 H, C6H5), 7.27−7.19 (m, 3 H, C6H5), 4.19 (m, 1 H,
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5
= 7.6 Hz, 2 H, CH2CH3), 1.73 (t, JHH = 2.5 Hz, 3 H, CH3), 1.19 (t,
3JHH = 7.6 Hz, 3 H, CH2CH3). 13C{1H} NMR (chloroform-d1, 100
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23
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ASSOCIATED CONTENT
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* Supporting Information
Synthetic, catalytic, and kinetics procedures, tables with HPLC
conditions, and data for evaluating optical purity, configuration
assignments. This material is available free of charge via the
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J. Am. Chem. Soc. XXXX, XXX, XXX−XXX