Page 554 - Advanced Organic Chemistry Part B - Reactions & Synthesis

528 most 1,3-dipolar compounds are not highly polar. The polarity implied by any single
structure is balanced by other contributing structures.
CHAPTER 6
Concerted .. .. ..
Cycloadditions, + N – R δ+ N δ– R N R
Unimolecular .. N C .. N C .. N C
Rearrangements, and R R R
Thermal Eliminations

6.2.1. Regioselectivity and Stereochemistry

Two issues are essential for predicting the structure of 1,3-DCA products:
(1) What is the regiochemistry? and (2) What is the stereochemistry? Many specific
examples demonstrate that 1,3-dipolar cycloaddition is a stereospecific syn addition
with respect to the dipolarophile, as expected for a concerted process.

Ph N N Ph cis -stilbene + – trans -stilbene Ph N N Ph
H H PhC N NPh H Ph
diphenylnitrilimine
Ph Ph Ph H
Ref. 138

Z-CH CH CHOC H E -CH CH CHOC H 7
3
3
N 3 3 7 – + N
O N N N O 2 N N N N O 2 N N N
2
H H H
p –nitrophenyl azide CH
3
OC H H OC H
CH 3 3 7 3 7
Ref. 139
With some 1,3-dipoles, two possible stereoisomers can be formed by syn addition.
These result from two differing orientations of the reacting molecules that are analogous
to the endo and exo TS in D-A reactions. Phenyldiazomethane, for example, can add
to unsymmetrical dipolarophiles to give two diastereomers.

H N Ph N
H CH Ph H N
– + 3 N +
PhCH N N + H CH H CH 3
CH O C CO 2 CH 3 3 CH O C CO CH
2
3
CH 3 O C CO CH 3 3 2 2 3
2
2
phenyldiazomethane
Ref. 140
Each 1,3-dipole exhibits a characteristic regioselectivity toward different types
of dipolarophiles. The dipolarophiles can be grouped, as were dienophiles, depending
upon whether they have ERG or EWG substituents. The regioselectivity can be

138
R. Huisgen, M. Seidel, G. Wallibillich, and H. Knupfer, Tetrahedron, 17, 3 (1965).
139 R. Huisgen and G. Szeimies, Chem. Ber., 98, 1153 (1965).
140
R. Huisgen and P. Eberhard, Tetrahedron Lett., 4343 (1971).