Page 217 - Advanced Organic Chemistry Part B - Reactions & Synthesis

The nitro group can be converted to a ketone by hydrolysis of the nitronate anion, 189
permitting the synthesis of 1,4-dicarbonyl compounds.
SECTION 2.6
O O Conjugate Addition by
1) LDA 10% HCl CH Carbon Nucleophiles
CH CH CCH CH 3 3 CH 3
2
2
3
2) CH 3
CH 2 CH 3 O 64%
NO 2
Ref. 302
Anions derived from nitriles can act as nucleophiles in conjugate addition reactions.
A range of substituted phenylacetonitriles undergoes conjugate addition to 4-phenylbut-
3-en-2-one.

O CN
H + CH 3
ArCHC N + PhCH CHCCH 3 [1,2-anion] [1,4-anion] Ar
Li Ph O

The reaction occurs via the 1,2-adduct, which isomerizes to the 1,4-adduct, 303 and
there is an energy difference of about 5 kcal/mol in favor of the 1,4-adduct. With the
parent compound in THF, the isomerization reaction has been followed kinetically and
appears to occur in two phases. The first part of the reaction occurs with a half-life of
a few minutes, and the second with a half-life of about an hour. A possible explanation
is the involvement of dimeric species, with the homodimer being more reactive than
the heterodimer.
–4 –1
–4 –1
k = 30 x 10 s k = 2 x 10 s
[1,2-anion] 2 [1,2-anion][1,4-anion] [1,4-anion] 2
A very important extension of the conjugate addition reaction is discussed in
Chapter 8. Organocopper reagents have a strong preference for conjugate addition.
Organocopper nucleophiles do not require anion-stabilizing substituents, and they
allow conjugate addition of alkyl, alkenyl, and aryl groups to electrophilic alkenes.

2.6.2. Conjugate Addition with Tandem Alkylation
When conjugate addition is carried out under aprotic conditions with stoichio-
metric formation of the enolate, the adduct is present as an enolate until the reaction
mixture is quenched with a proton source. It is therefore possible to effect a second
reaction of the enolate by addition of an alkyl halide or sulfonate to the solution of
the adduct enolate, which results in an alkylation. This reaction sequence permits the
formation of two new C−C bonds.
R 1 – R 1 R 3
3
R 1 – + EWG 2 1 2 R X 1 2
R 2 EWG EWG EWG EWG
EWG 1 R 2 R 2

302 M. Miyashita, B. Z. Awen, and A. Yoshikoshi, Synthesis, 563 (1990).
303
H. J. Reich, M. M. Biddle, and R. J. Edmonston, J. Org. Chem., 70, 3375 (2005).