Page 972 - Advanced Organic Chemistry Part B - Reactions & Synthesis

948 O
H
R H 2 O [R N C OH] + CO
CHAPTER 10 R RNH 2 2
C – :
Reactions Involving N : N C N: O C N R
Carbocations, Carbenes, O + O N H O
and Radicals as Reactive N
Intermediates N R'OH R N C OR'
The acyl azide intermediates are prepared either by reaction of sodium azide
with a reactive acylating agent or by diazotization of an acyl hydrazide. An especially
convenient version of the former process is treatment of the carboxylic acid with ethyl
chloroformate to form a mixed anhydride, which then reacts with azide ion. 265

O
O O – O
RCO H ClCOEt RCOCOC H N 3 RCN 3
2
2 5
O O
NaNO 2
RCNHNH 2
H + RCN 3
The transformation can also be carried out on the acid using diphenylphosphoryl azide
(DPPA). 266

O O O
R'OH
RCO H + (PhO) PN 3 RCN 3 RNHCOR'
2
2
This version of the Curtius rearrangement has been applied to the synthesis of amino
acid analogs and structures containing amino acids. Several cis-2-aminocyclopropane
carboxylate esters were prepared by selective hydrolysis of cyclopropane-1,2-
dicarboxylates, followed by reaction with DPPA. 267
O
1) NaOH, H 2
R 2) DPPA, i Pr NEt R
2
CH O C CO CH 3 t BuOH (CH ) CO CNH CO 2 CH 3
3 3
2
2
3
2
90–95°C 24–40%
R = alkyl, aryl
The Curtius reaction has occasionally been used in formation of medium 268 and large 269
rings, usually in modest yield.
O CH(CH 3 ) 2
O CH(CH 3 ) 2 CH 3 NH
DPPA O
CH 3 N
N CO 2 H i Pr 2 NEt C 7 H 15 H
C 7 H 15 N
H O 27 % yield
NHCH 3 CH 3
O 1:1 mixture
O OH CH 2 Ph
O OH CH 2 Ph of stereoisomers
265
J. Weinstock, J. Org. Chem., 26, 3511 (1961).
266
D. Kim and S. M. Weinreb, J. Org. Chem., 43, 125 (1978).
267 S. Mangelinckx and N. De Kimpe, Tetrahedron Lett., 44, 1771 (2003).
268 C. Hermann, G. C. G. Pais, A Geyer, S. M. Kuhnert, and M. E. Maier, Tetrahedron, 56, 8461 (2000).
269
Y. Hamada, M. Shibata, and T. Shioiri, Tetrahedron Lett., 26, 5155, 5159 (1985).