Curtius重排有机化学

then t-BuOH, reflux, 81% O
CbzN O
HN
O
H
O
N
N
OO
N H
N H
CO2H
H
Syringolin A
C. R. J. Stephenson et.al. Org. Lett., 2010, 12, 3453-3455
2.4 the synthesis of carbamates
3.2 Lossen Rearrangement
Mechanism of Lossen Rearrangement
3.2 Lossen Rearrangement
Recent applicationsLeabharlann OR1OH N
H
CDI MeCN
O
O O
R1 N
CDI: 羰基二咪唑
J. A. stafford. et.al. J. Org. Chem. 1998, 63, 10040
R1 N C O R2 NH2 Isocyanate
O
R1 N H
NHR2
Urea derivative
R2 OH
O
R1 N H
OR2
Carbamate
2.1 Mechanism
Thermal rearrangement
Photochemical rearrangement
注意：由于氮烯存在的证据很难找到，也有人认为 基团的迁移和N2的离去为一协同过程。
Curtius Rearrangment
Contents
1 Introduction 2 CurtiuCsliRckeatorrandgdeTmitelent 3 OtherCNliucckletoopahdidlicTritelearrangement 4 ConcClulsicioknto add Title
First published in 1881:
Hofmann, A. W. Chem. Ber. 1881, 14, 2725. Shioiri, T. Comp. Org. Syn. 1991, 6, 800‐806. (Review)
MOR or M(OR)2 MOX or NaBrO2
H2O / 0oC then heat
OMe OMe
OMe OMe
OO MeO
H OMe
1) 10% NaOH/MeOH, RT
HO
OH
2) DPPA, Et3N,
N Teoc
2-trimethylsilylethanol, 4-A MS, THF, reflux
H OMe
OH
75% (2 steps)
OMe OMe
MeO OH H O
2.3 the synthesis of ureas
A Solid-Phase Synthesis of N,N′-Disubstituted Ureas
M. T. Migawa.et.al. Org. Lett., 2000, 2, 3309-3311
H. Lebel, et.al. Org. Lett., 2006, 8, 5717-5720
Introduction
亲核重排（缺电子重排）
在缺电子重排反应中，基团Z带着一对电子从原子A迁移到另一个缺 少电子的原子B上，多数为1,2-重排，即基团的迁移在两个相邻原子 间发生：
常见的亲核重排类型
缺电子碳链的重排 Baeyer-Villiger oxidation rearrangement, Backman rearrangement, pinacol rearrangement 等.
2.3 the synthesis of ureas
T. G. Back et.al. J. Org. Chem., 2010, 75, 1612-1619 Y. Hisamatsu, et.al. Org. Lett. 2010, 12, 1776-1779
2.4 the synthesis of carbamates
2.2 the synthesis of amines
D. L. Boger et.al. J. Am. Chem. Soc. 2006, 128, 15683-15696. Olivier Baudoin et.al. Angew. Chem. Int. Ed. 2009, 48, 179 -182
3.3 Wolff Rearrangement
Wolff (1902)
Lossen Rearrangement
3.3 Wolff Rearrangement
Mechanism of Wolff Rearrangement
3.3 Wolff Rearrangement
Recent applications
N2
O
O NuH (1 equiv), PhMe
O
μ W ( 300 W), 1- 30 mi n
n
-N2
n
R
29 examples
R
O Nu
n = 0, 1, 2
Y. Coquerel. et.al. J. Org. Chem. 2009, 74, 415.
H. Yang. et.al. Org. Lett. 2000, 2, 2177.
55%
Ph N Ph
NH Cbz
1) H2, Pd(OH)2/C MeOH, HCl
2) o-anisaldehyde, NaBH(OAc)3, CH2Cl2
66%
H N Ph
NH OMe
2-Epi-CP-99,994
J. Szymoniak. et.al. Org. Lett., 2008, 10, 2473-2476
2.4 the synthesis of carbamates
O H
CbzN O
HO2C steps
Garnes's alde
K.Tomioka. et.al. Org. Lett., 2009, 11, 2007-2009
CbzN
DPPA, Et3N, 4A MS, toluene, rt
BocHN
O R1 C
N
CO2
HNR2 R3 R 4OH
O
R1 N H
NR2R3
O
R1 N H
OR4
P. Dube. et.al. Org. Lett. 2009, 11, 5622.
3.2 Lossen Rearrangement
Recent applications
K. Ohmoto. et.al. Synlett. 2001, 299.
Carda, M., Marco, J. A. Tetrahedron: Asymmetry, 2002, 13, 1005-1010. M. Lautens. et.al. J. Am. Chem. Soc. 2005, 127, 15028-15029.
2.4 the synthesis of carbamates
3.1 Hofmann Rearrangement
Recent applications
R. A. Hollingsworth. et.al. J. Org. Chem. 1999, 64, 1036
G. S. Kauffman. et.al. J. Org. Chem. 1997, 62, 6918
3.1 Hofmann Rearrangement
Recent applications
O PhIX2
R NH2
J. W. Keillor et.al. J. Org. Chem. 1997, 62, 7495.
OX I
R N Ph H
1,2-shift
N RC
O
H2O
R NH2
O O PhIX2 S
2. Curtius Rearrangement
O R1 OH
O SOCl2
R1 Cl
acid chloride
NaN3 TMSN3
H2O
R1 NH2 Amine
ClCO2Et
OO
NaN3
R1 O OEt
mixed anhydride
O heat
R1 N3 -N2 acyl azide
(PhO)2P(O)N3
O
N
OH
H
O OMe
pederin
J. C. Jewett, V. H. Rawal. Angew. Chem. Int. Ed. 2007, 46, 6502 -6504
F. Matsuda, et.al. Org. Lett., 2010, 12, 904-907
3.1 Hofmann Rearrangement
碳烯与氮烯的重排 Curtius rearrangement , Schmidt rearangement , Wolff rearrangement, Lossen rearangement , Hofmann rearrangement
Introduction
Julius Wilhelm Theodor Curtius (1957-1928), 德国化 学家，生于德国鲁尔区的Duisburng。先后师从Bensun和 Kolbe 。 1882 年 ， 在 Leipzig 大 学 取 得 博 士 学 位 。 1884 年，在慕尼黑大学跟随Baeyer工作。在1890年到1894年 间，发现了酰基叠氮化物的重排反应，并以其名字命名。 除此之外，他还发现了叠氮醋酸乙酯（1883），联氨 （1887），叠氮化合物（1891），吡唑啉衍生物（1891） 四嗪衍生物（1906），多肽（1904）。
3.3 Wolff Rearrangement
NHRN12
OR3
Rh2(OAc)4 2H2O, PhH, reflux.
R1 NO
Ar
S
OO
Ar S
CO2R3
K. Kim. et.al. Org. Lett. 2002, 4, 873.
N2 O
Br
OTIPS
HO
OTIPS
C
hν
O Br
Br
Me
DCE, rt; then 80oC
M = Na, K, Ba, Ca
X = Cl, Br
LTA or PhI(OCOR)2 or PhI(OH)OTs or
PhIO pH = 1-3 / solvent / H2O
LTA: 四乙酸铅
3.1 Hofmann Rearrangement
Mechanism of Hofmann Rearrangement
2.4 the synthesis of carbamates
D. H. Appella. et.al. J. Am. Chem. Soc. 2004, 126, 15067-15073
Ph
N Ph 1) TFA, CH2Cl2
O 2) DPPA, Et3N, toluene
3) BnOH
Ot-Bu
O O
NH
NH NH
1) LiOH, H2O, THF, H2O2 50oC, 12h, 92%
2) DIPEA, acetone, ClCO2Et, 0oC; NaN3, rt, 12h, 75%
O O
NH NH
NH NH
R. L. Funk et.al. Org. Lett., 2006, 8, 3995-3998
2.2 the synthesis of amines
Nakahara, S.et.al. J. Am. Chem. Soc. 1993, 115, 10733-10741. F. M. Menger.et.al. Angew. Chem. Int. Ed. 2002, 41, 2581 -2584.
O
Boc2O, NaN3
R OH Bu4NBr, Zn(OTf)2
THF, 40oC
H N Ot-Bu R
O yield 57%-94%
OH Boc2O, NaN3, Bu4NBr (15 mol%)
O
THF, 40oC
N3 no Zn(OTf)2
O
H. Lebel, O. Leogane. Org. Lett., 2005, 7, 4107-4110
R NH2
OO SX
R HN I Ph
1,2-shift
NO RS
O
H2O
RNHSO3H
-HX β - el i mi nat i onPhI NSO2R
M. Ochiai. et.al. J. Am. Chem. Soc. 2009, 131, 8392.
3.1 Hofmann Rearrangement
D. A. Evans. et.al. Org. Lett. 2001, 3, 3009-3012
D. ROmo. et.al. J. Am. Chem. Soc. 2003, 125, 6344
3.2 Lossen Rearrangement
W. Lossen (1872)
Lossen Rearrangement
+
71%
OTIPS
Me
Me
steps
O
O
Me Salvilenone
R. L. Danheiser. et.al. J. Am. Chem. Soc. 1994, 116, 9471.