Computational Chemistry

electrostatic potential charges (the G98 keyword Pop¼MK was used) again using
B3LYP/6-31+G*:

fk"ðSÞ¼qðS;anionÞ"qðS;neutralÞ¼ 16 : 720 " 15 : 955 ¼ 0 : 765

fk"ðCÞ¼qðC;anionÞ"qðC;neutralÞ¼ 5 : 542 " 5 : 707 ¼ 0 : 165

fk"ðNÞ¼qðN;anionÞ"qðN;neutralÞ¼ 7 : 738 " 7 : 338 ¼ 0 : 400

In this case the conclusions, compared to using AIM charges, are unaffected.
In an extensive study, Geerlings et al. [ 105 ] showed that with AIM charges
semiquantitatively similar results are obtained with a variety of correlation methods
(HF, MP2, QCISD, and five DFT functionals), using bases similar to 6-31G*. The
biggest deviation from QCISD (Section 5.4.3; QCISD was taken as the most reliable
of the methods used) was shown by MP2. For example, for CH 2 CHO"all correlation
methods except MP2 gave O a biggerf"than C. If we disregarded the MP2 result as
anomalous, this could be interpreted as indicating that the O is more nucleophilic than
the C. Actually, in standard organic syntheses enolates usually react preferentially at
thecarbon, but the ratio of C:O nucleophilic attack can vary considerably with the
particular enolate, the electrophile, and the solvent. To complicate things even more,
the nucleophile is not always just the simple enolate: an ion pair or even aggregates of
ion pairs may be involved [ 156 ]. Even for the case of an unencumbered enolate, the
atom with the biggestf"(the softest atom) cannot be assumed to be the strongest
nucleophilic center, because, as Me ́ndez and Ga ́zquez point out in their study [ 157 ] of
enolates using the Fukui function, one consequence of the hard-soft-acid-base prin-
ciple is that an electrophile tends to react with a nucleophilic center ofsimilar
softness (soft acids prefer soft bases, etc.), not necessarily with the softest nucleo-
philic center. Thus for the reaction of CH 2 CHO"with the electrophile CH 3 X, one
might calculate, for CH 2 CHO",f"(C) andf"(O), and for CH 3 X,fþ(C). The CH 3 XC
would be expected (in the absence of complications!) to bond to the atom, C or O,
whosef"value was closest to itsfþ(C) value. A study of the ethyl acetoacetate
enolate using these and other concepts has been reported by Geerlings and coworkers
[ 158 ]. This approach, which is applicable to any ambident species, is further illu-
strated below by the reaction of HNC with alkynes.
In a study of the reaction of alkynes with hydrogen isocyanide the condensed
Fukui function was combined with the overall or global softness to try to rationalize
the regioselectivity of attack on the triple bond [ 153 ]:

b? a?

C

N

H

C

N

H

b a

CH 3 C^2 C^1 H

H

+C C

CH 3

C–

N

H

B

CH 3

C C+

H

C–

N

H

A

506 7 Density Functional Calculations