Page 896 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

880 + – + – + – + – + – + –
HN N N H C N O H C N N HC N O HC N NH HC N CH 2
2
2
CHAPTER 10 azide nitrone diazoalkane nitrile oxide nitrile imine nitrile ylide
Concerted Pericyclic +1.8
Reactions + 0.9
+0.1 +0.1
– 0.5 – 0.5

–7.7
–9.0 –9.2
–9.7
–11.0
–11.5

Fig. 10.14. Estimated energies (eV) of frontier MOs for some 1,3-dipoles. Data from J. Am. Chem. Soc.,
95, 7287 (1973).

of the interacting orbitals, it is possible to make predictions of the regiochemistry
of 1,3-DPCA reactions. The most important dipolarophiles are the same types of
compounds that are dienophiles in the D-A reaction. The orbital coefficients given
in Figure 10.5 can be used in analyses of 1,3-DPCA reactions. In conjunction with
the orbital coefficients given in Figure 10.15, this information allows conclusions as
to which HOMO-LUMO combination will interact most strongly for a given pair of
reactants.
This procedure is illustrated for two specific cases in Figure 10.16. The reaction
of a nitrile oxide with an alkene is considered on the left. The smallest energy gap is for
the alkene HOMO and the 1,3-dipole LUMO. This is qualitatively reasonable in that
the atoms in the 1,3-dipole are more electronegative than those in the dipolarophile.
Reference to Figure 10.15 shows that the LUMO coefficient is largest at carbon for
the nitrile oxide group. The largest coefficient for a terminal alkene HOMO is at C(1).
The matching of the largest coefficients of the 1,3-dipole LUMO and the dipolarophile
HOMO leads to the predicted (and observed) product. The same procedure can be
applied to the case shown at the right of Figure 10.16. In this case, the 1,3-dipole is
the nucleophile and the dipolarophile is the electrophile. The largest coefficient of the
nitrone HOMO is at oxygen and the largest coefficient for the acrylate ester LUMO
is at the -carbon.
Although the FMO approach provides a good foundation for understanding
the regioselectivity of 1,3-cycloadditions, there are many specific cases in which it
fails to provide a complete understanding. Steric factors are not considered by the
FMO analysis and in many instances steric factors control regiochemistry. 1,3-DPCA
can be broadly classified as sterically controlled or electronically controlled. There
may also be specific interactions in the TSs that are not considered by the FMO
analysis.
There have been many studies of individual systems by MO and DFT methods and
these provide further insight into the factors that control regio- and stereoselectivity.
For example, there are two possible regioisomers from the reaction of diazomethane
and methyl vinyl ether, but only the 3-methoxy isomer is formed. Calculations at
∗
several levels of theory (AM1, HF/6-31G, and MP2/6-31G ) found lower activation