Page 200 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

180 The Cieplak model emphasizes an alternative interaction, between the orbital of
the C−X bond and the antibonding orbital to the nucleophile. 118 In this case, a better
CHAPTER 2 donor X should be the most stabilizing. Li and le Noble pointed out that both of these
Stereochemistry, hyperconjugative interactions will be present in the transition structure. 119 There is also
Conformation,
and Stereoselectivity general agreement that addition of reactive nucleophiles have early transition states,
which would suggest that substituent effects might best be examined in the reactant.
Nu
Nu

O
O
X X

Felkin-Ahn Model Cieplak Model

One broad generalization is that when steric interactions are dominant the Felkin-
Ahn model is predictive. Thus steric approach control, the idea that the approaching
nucleophile will approach the carbonyl group from the least hindered direction, is the
first guiding principle. 120
The TS model emphasizing steric effects must be elaborated when there is a
polar substituent in the vicinity of the carbonyl group. At least three additional factors
may then be involved. There are stereoelectronic effects associated with heteroatom
substituents. Electronegative substituents such as halogen are assigned to the l position
in the Felkin-Ahn TS on the basis of presumed stronger stereoelectronic interactions
∗
with the C=O bond. According to this analysis, the bond to the halogen stabilizes the
TS. An anti-periplanar arrangement maximizes this interaction. It is likely that there are
also electrostatic effects involved in controlling nucleophilic addition reactions, since
compounds such as decalones, 121 norbornan-7-ones, 122 and adamantanones, 123 which
have remote substituents that cannot directly interact with the reaction site, nevertheless
influence the stereoselectivity. It remains a point for discussion as to whether these
substituent effects are electrostatic in nature or are transmitted by hyperconjugation.
(See Topic 2.4 for further discussion.)
It should also be emphasized that the metal counterions associated with the
nucleophiles are active participants in carbonyl addition reactions. There are strong
interactions between the carbonyl oxygen and the metal ions in the TSs and interme-
diates. This effect can be recognized, for example, in the reactivity of borohydrides,
+
2+
where the Li ,Ca , and Zn 2+ salts are more reactive than the standard NaBH reagent
4
because of the greater Lewis acid strength of these cations.
The examples just discussed pertain to substituents that are on the carbon adjacent
to the carbonyl center and the stereoselectivity is referred to as 1,2-asymmetric
118
A. S. Cieplak, J. Am. Chem. Soc., 103, 4540 (1981).
119
H. Li and W. J. le Noble, Recl. Trav. Chim. Pays-Bas, 111, 199 (1992).
120 W. G. Dauben, G. J. Fonken, and D. S. Noyce, J. Am. Chem. Soc., 78, 2579 (1956); H. C. Brown and
H. R. Deck, J. Am. Chem. Soc., 87, 5620 (1965).
121
Y.-D.Wu, J. A. Tucker, and K. N. Houk, J. Am. Chem. Soc., 113, 5018 (1991).
122 G. Mehta and F. A. Khan, J. Am. Chem. Soc., 112, 6140 (1990); H. Li, G. Mehta, S. Padma, and W. J. le
Noble, J. Org. Chem., 56, 2006 (1991); G. Mehta, F. A. Khan, B. Ganguly, and J. Chandrasekhan, J.
Chem. Soc., Perkin Trans., 2, 2275 (1994).
123
C. K. Cheung, L. T. Tseng, M.-H. Lin, S.Srivastava, and W. J. Le Noble, J. Am. Chem. Soc., 108, 1598
(1986); J. M. Hahn and W. J. Le Noble, J. Am. Chem. Soc., 114, 1916 (1992).