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DOI: 10.1055/s-0029-1218545
Chiral Aziridination of Olefins Using a Chiral Sulfinamide as the Nitrogen Source
Publikationsverlauf
Publikationsdatum:
02. Dezember 2009 (online)
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Abstract
Chiral aziridination of cyclic α-bromoenones is achieved by the use of the lithium salt of (S S)-(+)-p-toluenesulfinamide, which leads to products with diastereomeric excesses in the range of 30-65% using a simple protocol. A key factor associated with chiral induction is the incorporation of the reacting olefin in a cycle, indicating the importance of conformational restriction in the reacting double bond.
Key words
aminations - chirality - cyclizations - enones - Michael additions
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References and Notes
This compound is commercially available from Sigma-Aldrich Co (http://www.sigmaaldrich.com).
17CCDC 741870 contains the crystallographic data which can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing data_request@ccdc.cam. ac.uk, or by contacting CCDC, UK; fax: +44 (1223)336033.
21Full coordinates and other information about the calculations can be found via the following digital repository entries: 10042/to-2308, 10042/to-23010, 10042/to-2311, 10042/to-2312, 10042/to-2314 and 10042/to-2315, resolved as e.g. http://dx.doi.org/10042/to-2308. An interactive version of this figure can be viewed via the HTML version of this article.
22
Typical Experimental
Procedure for Aziridination
To a dry THF solution
of 2-bromocyclohex-2-en-1-one (2a, 0.286
mmol), under nitrogen atmosphere and protected from light at -78 ˚C,
was added the lithium salt of chiral sulfinamide 1 (0.858
mmol) and the reaction allowed to reach r.t. After 30 min the solvent
was removed under reduced pressure and the residue dissolved in
EtOAc, washed with aq NH4Cl (10%), and after
drying and solvent removal, the remaining residue was purified via
silica gel PTLC (EtOAc-n-hexane,
1:1) to afford a mixture of the title aziridines 3Aa (major)/3Ba (minor); yield 62%. Separation of
both diastereomers was achieved by 2 × PTLC
of the mixture.
Compound 3Aa(major):
mp 70-71 ˚C (EtOAc-n-hexane); [α]D
²³ +64.6
(c 0.99, CHCl3).
Compound 3Ba(minor): mp 90-91 ˚C
(EtOAc-n-hexane); [α]D
²³ +89.4
(c 1.44, CHCl3). ¹H
NMR (400 MHz, CDCl3; 3Aa/3Ba = 77:23): δ = 7.60
(2 H, d, J = 8.2
Hz, minor), 7.55 (2 H, d, J = 8.2
Hz, major), 3.23 (1 H, d, J = 6.3
Hz, minor), 3.13 (1 H, d, J = 6.3
Hz, major), 3.06 (1 H, d, J = 6.3
Hz, major), 2.94 (1 H, d, J = 6.3
Hz, minor). MS (CI): m/z (%) = 249
(100) [M+]. Anal. Calcd for
C13H15NO2S: C, 62.62; H, 6.06;
N, 5.62. Found: C, 62.31; H, 6.34; N, 5.74.
Compound 3b: oil. ¹H NMR (400
MHz, CDCl3): δ = 7.59 (2 H, d, J = 8.1 Hz,
minor), 7.55 (2 H, d, J = 8.1
Hz, major), 3.08 (1 H, d, J = 6.3
Hz, major), 2.94 (1 H, d, J = 6.4
Hz, minor), 2.85 (1 H, d, J = 6.4
Hz, minor), 2.77 (1 H, d, J = 6.3 Hz,
major). HRMS: m/z calcd for
C15H19NO2S: 277.11365; found: 277.11344.
Anal. Calcd for C15H19NO2S: C,
64.95; H, 6.90; N, 5.05. Found: C, 65.27; H, 7.16; N, 4.95.
Compound 3c: mp 64-65 ˚C
(EtOAc-n-hexane). ¹H
NMR (400 MHz, CDCl3): δ = 3.79 (2 H,
d, J = 5.4
Hz, minor), 3.64 (1 H, d, J = 5.6
Hz, major), 3.41 (1 H, d, J = 6.2
Hz, major), 3.30 (1 H, d, J = 6.2
Hz, minor). MS (EI): m/z (%) = (1.1) 402 [M + 1]+.
Anal. Calcd for C25H23NO2S: C,
74.78; H, 5.77; N, 3.49. Found: C, 75.16; H, 5.74; N, 3.37.
Compound 3d (major): mp 97-98 ˚C
(Et2O-n-hexane); [α]D
²³ +22.0
(c 0.90, CHCl3).
Compound 3d (minor): mp 105-106 ˚C
(Et2O-n-hexane); [α]D
²³ +12.4
(c 2.03, CHCl3). ¹H
NMR (400 MHz, CDCl3): δ = 7.62 (2 H,
d, J = 8.2
Hz, minor), 7.54 (2 H, d, J = 8.2
Hz, major), 3.56 (1 H, m, minor), 3.53 (1 H, m, major), 3.11 (1 H,
d, J = 4.3
Hz, major), 3.08 (1 H, d, J = 4.3
Hz, minor). HRMS-FAB: m/z calcd
for C12H14NO2S: 236.074526; found:
236.075172.
Compound 3f: oil. ¹H
NMR (400 MHz, CDCl3): δ = 7.60 (2 H,
d, J = 7.8
Hz, minor), 7.54 (2 H, d, J = 7.8
Hz, major), 3.23 (1 H, d, J = 4.4
Hz, minor), 3.21 (1 H, d, J = 4.4
Hz, major), 3.13 (1 H, d, J = 4.4
Hz, major), 3.10 (1 H, d, J = 4.4 Hz,
minor). MS (FI): m/z (%) =(100)
263 [M+]. Anal. Calcd for
C14H17NO2S: C, 63.85; H, 6.51;
N, 5.32. Found: C, 62.95; H, 6.81; N, 5.17.
Compound 3g: mp 92-93 ˚C
(Et2O-n-pentane). ¹H
NMR (400 MHz, CDCl3): δ = 7.61 (2 H,
d, J = 8.1
Hz, minor), 7.56 (2 H, d, J = 8.1
Hz, major), 3.13 (1 H, J = 7.7,
1.5 Hz, major), 3.06 (1 H, m, minor), 2.97 (1 H, dd, J = 7.7, 4.6
Hz, major), 2.80 (1 H, m, minor). MS (EI): m/z (%) =(18)
263 [M+]. Anal. Calcd for
C14H17NO2S: C, 63.85; H, 6.51;
N, 5.32. Found: C, 62.62; H, 6.72; N, 5.29.
Compound 3h: diasteriomeric mixture (1:1), mp 69-71 ˚C, 77-80 ˚C
(EtOAc). ¹H NMR (400 MHz, CDCl3): δ = 2.81
(1
H, d, J = 4.1
Hz), 2.79 (1 H, d, J = 7.3
Hz), 2.71 (1 H, d, J = 6.9
Hz), 2.24 (1 H, d, J = 3.7
Hz). HRMS (EI): m/z calcd for
C16H15NO2S: 285.08235; found: 285.083598.
Anal. Calcd for C16H15NO2S: C,
67.34; H, 5.30; N, 4.91. Found: C, 67.34; H, 5.30; N, 4.91.
Compounds 3i: 3Ai: mp 103-105 ˚C
(EtOAc); [α]D
²³ -15.1 (c 3.30, CHCl3). ¹H
NMR (400 MHz, CDCl3): δ = 3.91 (1 H, dd, J = 6.5, 3.3
Hz), 2.89 (1 H, d, J = 3.3
Hz), 2.66 (1 H, d, J = 6.5
Hz). Anal. Calcd for C15H15NO3S2:
C, 56.05; H, 4.70; N, 4.36. Found: C, 55.87; H, 4.76; N, 4.38. 3Bi: mp 120-121 ˚C
(EtOAc); [α]D
²³ +7.4
(c 2.04, CHCl3). ¹H
NMR (400 MHz, CDCl3): δ = 3.70 (1 H,
dd, J = 6.3,
3.2 Hz), 2.75 (1 H, d, J = 6.3
Hz), 2.43 (1 H, br d); the attribution to 3Ai and 3Bi may be reversed. HRMS (EI): m/z calcd for C15H15NO3S2: 321.04933;
found: 321.04958.
Oxidation of 3Aa/3Ba
To
a solution of 3Aa/3Ba (0.2
mmol) was added MCPBA (0.4 mmol), and after 18 h at r.t. the solvent
was removed and the enantiomeric mixture of 4Aa/4Ba isolated (yield 99%); ee 53% from ¹H
NMR (400 MHz, CDCl3): δ = 3.45 (1 H,
H2) split by addition of Eu(hfc)3.