stereoselective routes to aziridines nate bowling mcmahon group university of wisconsin-madison...
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Stereoselective Routes to Aziridines
Nate Bowling
McMahon Group
University of Wisconsin-Madison
Sept. 12, 2002
Summary• Applications
– Uses for Optically Active Aziridines• Addition of Nitrogen to Alkenes
– Nitrenes– Atkinson-type Aziridinating Agents– Asymmetric Aziridination Catalysis
• Aziridinations using Already Existing Stereocenters– Sharpless Asymmetric Epoxidation and Dihydroxylation – Amino Alcohols
• Other Routes to Stereoselectivity– Imines– Michael Addition– Azirines
• Resolution
The Basics of Aziridines
• Ring Strain (SE) of 26.7 kcal/mol (R1-5 = H) – Oxirane = 26.3 kcal/mol – Cyclopropane = 27.5 kcal/mol
• Inversion barrier of nitrogen (R1-5 = H) = 18.9 kcal/mol – Normal amines = 5- 6 kcal/mol
• Usually only susceptible to ring opening by nuclephilic attack upon activation by: – Protonation– Quaternization – Lewis acid adduct – R5 = electron withdrawing substituent
N
R1 R2R3 R4
R5
Tanner, D. Angew. Chem. Int. Ed. Engl. 1994, 33, 599-619. Nielsen, I. M. B. J. Phys. Chem. A 1998, 102, 3193-3201.Bach, R. D.; Dmitrenko, O. J. Org. Chem. 2002, 67, 3884-3896.
Uses of Optically Active Aziridines
Stereocontrolled Synthesis of Alpha and Beta Amino Acids Through Aziridines
N
R2
R1 CO2R3
1
23* *
Nuc-
Nuc-
C-3 attack
C-2 attack
Nuc
R1
HNR2
CO2R3* *
-amino acid
R2NH
R1
Nuc
CO2R3* *
-amino acid(R2: electron-withdrawing group)
Dubois, L.; Dodd, R. H. Tetrahedron 1993, 49, 901-910.
Stereocontrolled Formation of β-Substituted Phenyl Amino Acids
Ph OBzl
O
HNOBzl
O
Ph OBzl
O
Ph OH
O
Ph OBzl
O
NHAc
OH
NH2
NHBoc
NH2
S
H3CO
Ph
NH
i) CH2Cl2, BF3.Et2O, p-MeOC6H5CH2SH, 67%
ii) (Boc)2O, TEA/THF, 90%
BF3.Et2O, indole, 48%
CH2Cl2 acetic acid, 70oC, 88%
H2, MeOH, 10% Pd-C, 90%
Xiong, C.; Wang, W.; Cai, C.; Hruby, V. J. J. Org. Chem. 2002, 67, 1399-1402.
Carbapenem Antibiotics Through a β-Lactam Ring Closing
N
H
Me
R1
COOH
S NHR2
O
HO
N
TsOR
LiEt2Cu, Et2O, 80%
NHTsHO
EtOR
HO2C NHTs
EtOR
RuCl3 (2 mol%) NaIO4
CCl4/CH3CN/H2O, RT, 82%
DCC, 4-pyrrolidino-pyridine (cat.)CH2Cl2, RT, 15 min, 83%
NO Ts
Et ORi) Na-napthalene, DME, -78°C, 85%ii) HCl, MeOH, RT, 91%
NO H
Et OHRuCl3 (2 mol%) NaIO4
CCl4/CH3CN/H2O, RT, 82%NO H
Et CO2H
Thienamycin R1 = OH R2 = H
PS-5 R1 = H R2 = Ac
R = SiPh2tBu
Tanner, D.; Somfai, P. Tetrahedron 1988, 44, 619-624.
Proposed Mode of Action of Mitomycin C
N
O
O
N H
OCH3H2N
H3C
CH2OC(O)NH2
N
OH
OH
N H
OCH3H2N
H3C
CH2OC(O)NH2EnzRedn
N
O
OH
N H
H2N
H3C
CH2OC(O)NH2
H
- MeOH
N
O
OH
H2N
H3C
CH2OC(O)NH2
NH2N
OH
OH
H2N
H3C
CH2OC(O)NH2
NH2
DNAN
OH
OH
H2N
H3CNH2
DNA
Na, Y.; Wang, S.; Kohn, H. J. Am. Chem. Soc. 2002, 124, 4666-4677.
Asymmetric Dihydroxylation with Aziridines
OsO4, LigandToluene, -78oC
OH
OH
NNPh
Ph
Ph
Ph
Yield = 90% ee = 95%
OH
OH
OH
OH
ent-Ligand Ligand
OsO4
OsO4
Ph
Ph
Ph
Ph
Ligand =
Tanner, D.; Harden, A.; Johansson, F.; Wyatt, P.; Andersson, P. G. Acta Chem. Scand. 1996, 50, 361-368.
Nitrenes
R N
Nitrene Addition in Accordance with Skell’s Rule
R N + N
R
HH3CCH3H
SingletNitrene
StereospecificAddiditon
+ N
R
CH3H3CHH
R N
TripletNitrene
+ N
R
HH3CCH3H
N
R
CH3H3CHH+
+
+ N
R
HH3CCH3H
N
R
CH3H3CHH
Non-stereospecifcAddition
McConaghy, J. S.; Lwowski, W. J. Am. Chem. Soc. 1967, 89, 2357-2364.
Different Reaction Pathways of Singlet and Triplet Nitrenes
Mishra, A.; Rice, S. N.; Lwowski, W. J. Org. Chem. 1968, 33, 481-486.
Mol % isoprene in CH2Cl2
Yield % Ratio A:B
100 95 2 1.17 0.05
30 86 3 1.21 0.03
2.5 87 1 1.45 0.02
0.5 85 2 2.13 0.05
EtO2CN3 N
CO2Et
N
CO2Et+
A B
hEtO2CN
N
CO2Et
α-Elimination, Irradiation, and Thermal Syntheses of Nitrenes
NEt3 or CaO or K2CO3N CO2R
O2N S
O
O= Ns
NH
O
O
RNsO
h or
ORN3
O
Fioravanti, S.; Loreto, M. A.; Pellacani, L.; Tardella, P. A. Tetrahedron Lett. 1993, 34, 4353-4354.Fioravanti, S.; Pellacani, L.; Stabile, S.; Tardella, P. A. Tetrahedron 1998, 54, 6169-6176.Bergmeier, S. C.; Stanchina, D. M. J. Org. Chem. 1997, 62, 4449-4456.McConaghy, J. S.; Lwowski, W. J. Am. Chem. Soc. 1967, 89, 2357-2364.Mishra, A.; Rice, S. N.; Lwowski, W. J. Org. Chem. 1968, 33, 481-486.
Highly Diastereoselective Nitrene Addition
NPhO2S
O
O
Ph
a b
O
CO2Ra
O
CO2Rb
NsONHCO2R
NsONHCO2R
CaO, CH2Cl2
CaO, CH2Cl2
R = Et, t-Bu
OCO2Rb
N CO2Et
OCO2Ra
N CO2t-Bu
OCO2Ra
N CO2Et
OCO2Rb
N CO2t-Bu
yield (%) de (%)
91
90
92
90
99
99
97
98
Fioravanti, S.; Morreale, A.; Pellacani, L.; Tardella, P. A. J. Org. Chem. 2002, 67, 4972-4974.
The Thermolysis of Several Different Species Gives One Common Nitrene
PhthalN N
N
PhthalN N
H
R
SMe2
PhthalN N
= Phthal
NPhthal
N
O
O
Atkinson, R. S.; Jones, D. W.; Kelly, B. J. J. Chem. Soc., Perkin Trans. 1 1991, 1344-1346.
Atkinson-type Aziridinating Agents
N
OO
NH2
N
O
O
NH2N
N
N
R
NH2
N
N
O
R
NH2
O
NH2
Atkinson, R. S.; Rees, C. W. J. Chem. Soc. (C) 1969, 772-778.Anderson, D. J.; Gilchrist, T. L.; Horwell, D. C.; Rees, C. W. J. Chem. Soc. (C), 1970, 576-579.
Oxidation of Atkinson-type Aziridinating Agents Gives Stereospecific Addition
Atkinson, R. S.; Rees, C. W. J. Chem. Soc. (C) 1969, 772-778.Anderson, D. J.; Gilchrist, T. L.; Horwell, D. C.; Rees, C. W. J. Chem. Soc. (C), 1970, 576-579.
NR2 NH2Pb(OAc)4
NR2 N
R1
R3 R4
R2
N
NR2
R3 R4
R1R2
Stereospecific Addition
Singlet stabilized by resonance
N NR2 N NR2
Invertomers
When X is electron withdrawing, the inversion
barrier is decreased. When X is electron donating,
the inversion barrier is increased.
NRX
NR
X
cis-invertomer trans-invertomer
H H
Atkinson, R. S.; Malpass, J. R. J. Chem. Soc., Perkin Trans. 1 1977, 2242-2249.
Kinetic v. Thermodynamic Invertomer Formation
N
O
N
O
N
O
N
O H
N
O
O
NH2 +
+ CO2Me
N
HC6H5
PhthalH
HN
HC6H5
HH
N
HMeO2C
PhthalH
HN
HMeO2C
HH
N
O
O
= Phthal
Phthal
Phthal
Top ViewLTA = Lead Tetraacetate
Pb(OAc)4, -20oC
Pb(OAc)4, -20oC
>0oC
>0oC
Atkinson, R. S. Tetrahedron 1999, 55, 1519-1559.
Non-bonding Interactions
OCH3
O
N
O
O
N N
O
N
OCH3
O
N
O
N
O
N
O
NH2
O O
Carbonyl-Carbonyl interactions
N
O
NH2
O
N
O
N
O
-stacking
OCH3
O
N
O
NH2
O
//+ O
O
Locked in s-trans conformation
Pb(OAc)4
Pb(OAc)4
Pb(OAc)4
Atkinson, R. S.; Grimshire, M. J.; Kelly, B. J. Tetrahedron 1989, 45, 2875-2886.
Alternative Intermediate
• Oxidation with Pb(OAc)4 at –20oC, and subsequent examination by NMR spectroscopy at -30oC revealed no presence of aziridine, but amino protons had disappeared.
• Removal of Pb(OAc)4 from solution revealed the presence of a methyl singlet that had previously been overshadowed by the Pb(OAc)4 acetate signal.
• Surmised that the reacting intermediate may not be nitrene, but acetoxyamino group instead.
Atkinson, R. S.; Grimshire, M. J.; Kelly, B. J. Tetrahedron 1989, 45, 2875-2886.
N
N
O
NH2
Me
N
N
O
NH
MeOAc
Mechanistic Pathway from Proposed Intermediate
Atkinson, R. S.; Williams, P. J. J. Chem. Soc., Perkin Trans. 1 1996, 1951-1956.
NH
OQ
Me
Ph
O
N
OQ
Me
O
OH
H3CO
Q =N
N
O
R
Support for the Proposed Mechanism
NN
Et
N
O
MeO
O
H
O
H O
H
H
iPr
H3CO
iPrHO
CO2Me
NN
Et
N
O
O
H
H3CO
NN
Et
N
O
O
H
H3CO
+
High diastereoselectivity
+
MeO2C
HOiPr
NN
Et
N
O
MeO
OH
O
H
H3CO
iPr
OH
Departure of Acetatefacilitated by alchol
Low diastereoselectivity
Departure not facilitatedby alcohol
Atkinson, R. S.; Williams, P. J. J. Chem. Soc., Perkin Trans. 1 1996, 1951-1956.
Stereochemical Control with the Aziridinating Agent
Atkinson, R. S.; Coogan, M. P.; Lochrie, I. S. T. Tetrahedron Lett. 1996, 37, 5179-5182.
N
N
O
Me
OSiMe2tBu
+Ph
TMS
N
H TMSPh H
d.r. 11:1
Q*
NH2
N
N
O
Me
OSiMe2tBu
Q* =
Diastereoselectivity Using Oppolzer’s Auxiliary
N
O
O
NH
OAc
+NH
SO2
Cl
O
R3
R1
R2 NSO2
O
R3R2
R1
Xc N
O R1 R2
R3 PhthalXc N
O R1 R2
R3 Phthal+
(major) (minor)
Ti(OiPr)4O
N
O R1 R2
R3 NPth
Kapron, J. T.; Santarsiero, B. D.; Vederas, J. C. J. Chem. Soc., Chem. Commun. 1993, 1074-1076.
R1 R2 R3 % Yield % de
H H H 94 78
H Ph H 90 80
Asymmetric Aziridination Catalysts
Catalytic Aziridination via Nitrenoid Intermediate
L*Cu+ PF6-
[L*Cu=NTs]+
PF6-
PhI=NTs
PhIR1 R3
R2
N
Ts
R1
R2
R3
Li, Z.; Quan, R. W.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5889-5890.
Nitrenoid intermediate allows for asymmetric aziridination under the influence of L*
Jacobsen Asymmetric Aziridination Catalyst
NNH H
Cl Cl
Cl Cl
OMe
Me
NC
PhI=NTs+L*.CuPF6
25oC
L* =
PhI +
OMe
Me
NCN
Ts
aziridine ee (%): 82-85
Li, Z.; Quan, R. W.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5889-5890.
Enantioselective Katsuki Aziridination Catalyst
Me Me
N N
O OPh Ph
Mn
AcO-
+ PhI=NTscatalyst (5 mol%), 4-phenylpyridine N-oxide
substrate-CH2Cl2 (5:1)
NTs
Nishikori, H.; Katsuki, T. Tetrahedron Lett. 1996, 37, 9245-9248.
Substrate Yield (%) % ee
Styrene 76 94
p- chlorostyrene 70 86
p-methylstyrene 75 81
Stereoselective Routes to Aziridines Using Sharpless
Asymmetric Epoxidation and Asymmetric Dihydroxylation
Catalysts
Sharpless Asymmetric Epoxidation
OH
R AE
(-)-tartrate
(+)-tartrate
AE
(+)-tartrate
(-)-tartrate
R OH
O
O
O
O
R
R
R
R
OH
OH
OH
OH
HN
NH
HN
NH
R
R
R
R
OH
OH
OH
OH
Tanner, D. Angew. Chem. Int. Ed. Engl. 1994, 33, 599-619.
Epoxide to Aziridine via Staudinger reaction
OH
RO NaN3
N3
OHH
RO+
OH
RO
N3H
PPh3CH3CNreflux
N
OHH
RO
OH
RO
NH
PPh3
PPh3
+
RO
H O
NH
PPh3
RO
HHN
OPPh3
+
RO
NHH
Sommerdijk, N. A. J. M.; Buynsters, P. J. J. A.; Akdemir, H.; Geurts, D. G.; Nolte, R. J. M.; Zwanenburg, B. J. Org. Chem. 1997, 62, 4955-4960.
Epoxide to Aziridine via Aza-Payne Reaction
ONH
Ts5% aq. NaOH solutionreflux5 min
N TsHO
PhOH
NO
H HTi(O-iPr)4THF, 0oC
63%Ph
OH
OHN
H
Urabe, H.; Aoyama, Y.; Sato, F. Tetrahedron 1992, 48, 5639-5646.Moulines, J.; Charpentier, P.; Bats, J.-P.; Nuhrich, A.; Lamidey, A.-M. Tetrahedron Lett. 1992, 33, 487-490.
Retention of Epoxide Configuration
O
R2R1
ArSNa
R2R1
OH
ArS
HO
SAr
R2
R1+
R2R1
NHTs
ArS
TsHN
SAr
R2
R1
+
TsNH2, BF3.Et2O
Me3O+ BF4-
R2R1
NHTs
ArS
TsHN
SAr
R2
R1+
Me Me
NaH
N
R2R1
Ts
Toshimitsu, A.; Abe, H.; Hirosawa, C.; Tamao, K. J. Chem. Soc., Perkin Trans. 1 1994, 3465-3471.
Sharpless Asymmetric Dihydroxylation
R
R'
AD-mix-
AD-mix-
HO OH
R R'
HO OH
R R' SOCl2
SOCl2O
SO
O
R R'
OS
O
O
R R'
OS
O
R R'
OS
O
R R'
O O
OO
RuO4
RuO4
1) LiN3
2) LiAlH4
1) LiN3
2) LiAlH4
NR
R'
H
N R'
R
H
Tanner, D. Angew. Chem. Int. Ed. Engl. 1994, 33, 599-619.
Different Pathways From Homochiral 1,2-Cyclic Sulfates
R'R''
OH
OHR'
R''
O
O
SO
O1) SOCl2
2) RuO4
LiN3, THF
R'R''
OSO3-Li+
N3
1) LiAlH4, THF,
2) 20% KOHR'
R"N
H
RNH2
THF, R'R''
OSO3-
NH2R
n-BuLi orLiAlH4, THF,or NaOH,
80-88%R'
R"N
R
62-89%
R'R''
OH
NHR
74%
1) 20% H2SO42) NaOH
Lohray, B. B.; Gao, Y.; Sharpless, K. B. Tetrahedron Lett. 1989, 30, 2623-2626.
Chiral Aziridines from Amino Alcohols
Okawa’s Aziridination Procedure From Amino Alcohols
H2N C
H2C OH
COOBzlTri-Cl
H
N C
H2C OH
COOBzl
H
Tr
H
Ts-ClPyridine N C COOBzl
H
Tr
H2C
Nakajima, K.; Takai, F.; Tanaka, T.; Okawa, K. Bull. Chem. Soc. Jpn. 1978, 51, 1577-1578.
Mitsunobu Reaction: Amino-Alcohol to Aziridine
R1 R2 R3 R4 time/solvent Yield (%)
C6H5CH2 H H CH3 2 h/ether 90
C6H5CH2 CH3 CH3 H 18 h/ether 89
R1 N C
H
R3C
R4OH
R2
NR1
R2
R3
R4
H DEAD, P(Ph)3
Pfister, J. R. Synthesis 1984, 969-970.
Preparation of Aziridines from the Mitsunobu Reaction of 1,2-Aminoalcohols
BnO N
H
HN
O
O HOHH3C
HNH
O
CH3 BnO N
H
N
O
O HNH
O
CH3
H3C H
Ph3P, DIAD
CH2Cl2, 0oC
56%
BnO O
NH
O
HN
NH
CH3
O
HOHH3C
HPh3P, DIADTHF, 0oC
BnO O
NH
O
NNH
CH3
O
HHH3C84%
Wipf, P.; Miller, C. P. Tetrahedron Lett. 1992, 33, 6267-6270.
Stereoselective Formation of Aziridines from Imines
General Mechanism of Aziridine Formation from Imines
N
R'
N
R'
MR"
X
O
OR
R"O
OR
X
M
R' OR
ON
R"
From alpha-halo enolates
From sulfonium ylides
N
R'
R"
CSR2H
N
R'
R"
SR2
Ph
Ph
PhN
R"
R'
High Diastereoselectivities From Sulfinimines in an Aza-Darzens Reaction
p-TolylS
N
O H
R1
H
X
OR2
OM
X = BrR2 = Me, t-Bu
OLi
OMe
R3
R1 = Ph
N
R1
H
CO2R2
SOp-Tolyl
+ N
H
R1
CO2R2
SOp-Tolyl
H H
N
Ph
H
R3
SOp-Tolyl
CO2Me+
N
Ph
H
CO2Me
SOp-Tolyl
R3
Major
Major (R3 = H)
Br
Davis, F. A.; Liu, H.; Zhou, P.; Fang, T.; Reddy, G. V.; Zhang, Y. J. Org. Chem. 1999, 64, 7559-7567.
R1 R3 R2 Conditions % de Yield (%)
Ph H Me LiHMDS/-78/2.5h
98 70
p-MeOPh H Me LiHMDS/-78/2.5h
98 74
Rationale for Diastereoselectivity
Davis, F. A.; Liu, H.; Zhou, P.; Fang, T.; Reddy, G. V.; Zhang, Y. J. Org. Chem. 1999, 64, 7559-7567.
Li
O
N
OMe
N
Ph
H
CO2Me
SOp-Tolyl
H
Ph
Br
SO
Ar
Li
O
N
OMe
Ph
Me
SO
Br
Ar
N
Ph
H
Me
SOp-Tolyl
CO2Me
Enantioselectivity Using the Imino Corey-Chaykovsky Reaction
S
p-Tolyl
OHR1 CH2Br
R2CH=NR3
+base, solvent
HN
H R1
R2 H
R3 = Ts
Saito, T.; Sakairi, M.; Akiba, D. Tetrahedron Lett. 2001, 42, 5451-5454.
R1 R2 Yield (%) trans:cis Trans ee(%)
Ph Ph >99 75:25 92
P-NO2C6H4 Ph >99 65:35 98
Highly Diastereoselective Aziridination of Imines with Trimethylsilyldiazomethane
NR2
R1
+N2
SiMe3 1,4-dioxane
40oC, 3-15hN
R1 SiMe3
R2
R2 = Ts
Aggarwal, V. K.; Alonso, E.; Ferrara, M.; Spey, S. E. J. Org. Chem. 2002, 67, 2335-2344.
R1 Yield (%) cis:trans
Ph 72 95:5
P-OMePh 65 100:0
Ring Closing Pathway
NR2
R1
+N2
SiMe3
Me3Si
H N2
N
R1 H
R2
ring closure H migration andprotodesilylation
N
R1 SiMe3
R2
NR2
R1
Aggarwal, V. K.; Alonso, E.; Ferrara, M.; Spey, S. E. J. Org. Chem. 2002, 67, 2335-2344.
Rationale for Cis-Selectivity
NR2
R1
+N2
SiMe3
Me3Si
H N2
N
R1 H
R2
NR2
R1
+N2
SiMe3
TMS
N2 HN
R1H
R2
TMS
H N2
N
R1H
R2
cis
trans
Aggarwal, V. K.; Alonso, E.; Ferrara, M.; Spey, S. E. J. Org. Chem. 2002, 67, 2335-2344.
Utilization of Michael Addition in Aziridine Synthesis
Highly Diastereoselective, Auxiliary Mediated, Gabriel-Cromwell reaction
S
N
O
HO O
Br2
S
N
O
BrO O
Br
*
S
N
O
BrO O
Et3N
S
N
O
BrO O
NH
R
H
RNH2
si-faceprotonation
S
N
O
O O
RNH
BrH
SN2
S
N
O
O O
N
R
H
R = Bn (86%),100%selectivityR = p-C6H4OMe (89%) dr = 9:1R = H (60%), 100%selectivity
Garner, P.; Dogan, O.; Pillai, S. Tetrahedron Lett. 1994, 35, 1653-1656.
Aziridines from Azirines
Synthesis of Optically Active Azirines via the Neber Reaction
N
N
OCH3
HHO
HN
N
OCH3
HHO
H H
TsO-
R OR'
N OTsO
N
R OR'
O
*
K2CO3 (s)KHCO3 + KOTs
R OR'
O O1) NH2OH.HCl, NaOH MeOH/H2O
2) TsCl, pyridine CH2Cl2
R OR'
N OTsO
NEt3CH2Cl2
N
R OR'
O
General
Enantioselective
Verstappen, M. M. H.; Ariaans, G. J. A.; Zwanenburg, B. J. Am. Chem. Soc. 1996, 118, 8491-8492.
Enantioselective Conversion of Neber Derived Azirines to Aziridines
R OR'
O O1) NH2OH.HCl, NaOH MeOH/H2O
2) TsCl, pyridine CH2Cl2
R OR'
N OTsO
N
R OR'
OBase
N
HCOOR'
R
NaBH4HN
H H
COOR'R
Exclusive formation of cis-aziridine carboxyic esters
Verstappen, M. M. H.; Ariaans, G. J. A.; Zwanenburg, B. J. Am. Chem. Soc. 1996, 118, 8491-8492.
R R’ Base Yield (%) ee (%)
Me Me Quinidine 40 81 (R)
Me Et Quinidine 43 82 (R)
Optically Active Aziridines via Resolution
Optical Resolution by Complexation with Optically Active Compounds
O
O
C
CPh
PhPh
OH
OH
Ph
O
O
C
C
OH
OH
Ph
PhPh
Ph
1a
1b
N N NR R RCO2Et CO2Me CO2Me
Me
2a R = Et2b R = nPr
2c R = Et2d R = nPr
2e R = nPr2f R = iPr
Mori, K.; Toda, F. Tetrahedron: Asym. 1990, 1, 281-282.
host yield (%) % ee2a 1a 34 1002b 1a 32 not determined2c 1b 43 642d 1b 44 1002e 1a 28 1002f 1a 33 100
Optical Resolution Through Lipase-Catalysed Alcoholysis
R1 R2 LipaseRxn time (days) ee substrate ee product
Total yield (%)
CH3 CH3 PPL 2 62.3 66 95iso-Pr CH3 PPL 42 5 54.5 50iso-Pr CH3 CCL 5 21 32 61iso-Pr CH2CF3 PPL 48 10 >95 73iso-Pr CH2CF3 CCL 10 91 68 90
N
R1
LipaseHexane, 40oCn-Butanol
OR2
O
N
R1
OR2
O
*N
R1
O-nBu
O
+ *
PPL = pig pancreatic lipaseCCL = Candida cylindracea lipase
Martres, M.; Gil, G.; Meou, A. Tetrahedron Lett. 1994, 35, 8787-8790 .
Review of Routes to Chiral Aziridines• Addition of Nitrogen to Alkenes
– Nitrenes– Atkinson-type Aziridinating Agents– Asymmetric Aziridination Catalysis
• Aziridinations using Already Existing Stereocenters– Sharpless Asymmetric Epoxidation and Dihydroxylation – Amino Alcohols
• Other Routes to Stereoselectivity– Imines– Michael Addition– Azirines
• Resolution
Acknowledgements• People who attended my practice talk:
- Jodie Brice- Matt Bowman- Reagen Miller- Greg Hanson- Jeff Johnson- Seol Kim- Beatriz DeGuia- Wendy deProphetis- Susie Przbylinski
• Special thanks to:– Wendy (computer, abstract)– Greg (abstract)– Juli