Page 164 - Advanced Organic Chemistry Part B - Reactions & Synthesis

136 Scheme 2.10. (Continued)

CHAPTER 2 9 i O O
CH 3 CH 3
CH 3 CH 3
Reactions of Carbon
Nucleophiles with HO CH 3 CH 3
Carbonyl Compounds O TiCl 4 HO O
CH 3 –78° CH 3
O O O
HO CH 3 65%
CH OTMS H
CH 3
O
a. J. English and G. W. Barber, J. Am. Chem. Soc., 71, 3310 (1949).
b. A. I. Meyers and N. Nazarenko, J. Org. Chem., 38, 175 (1973).
c. K. Wiesner, V. Musil, and K. J. Wiesner, Tetrahedron Lett., 5643 (1968).
d. G. A. Kraus, B. Roth, K. Frazier, and M. Shimagaki, J. Am. Chem. Soc., 104, 1114 (1982).
e. K. Yamada, H. Iwadare, and T. Mukaiyama, Chem. Pharm. Bull., 45, 1898 (1997).
f. J. K. Tagat, M. S. Puar, and S. W. McCombie, Tetrahedron Lett., 37, 8463 (1996).
g. M. D. Taylor, G. Minaskanian, K. N. Winzenberg, P. Santone, and A. B. Smith, III, J. Org.
Chem., 47, 3960 (1962).
h. A. Armstrong, T. J. Critchley, M. E. Gourdel-Martin, R. D. Kelsey, and A. A. Mortlock, J.
Chem. Soc., Perkin Trans. 1, 1344 (2002).
i. A. B. Smith, III, A. T. Lupo, Jr., M. Ohba, and K. Chen, J. Am. Chem. Soc., 111, 6648 (1989).

vinyl ketone or a similar enone. This is followed by cyclization by an intramolecular
aldol addition. Dehydration usually occurs to give a cyclohexenone derivative.

O
conjugate
CH CCH CH 2 addition H C CH 2 aldol addition
2
3
and
C O dehydration O
O
– O CH 3
Other , -unsaturated enones can be used, but the reaction is somewhat sensitive to
substitution at the -carbon and adjustment of the reaction conditions is necessary. 172
Scheme 2.11 shows some examples of Robinson annulation reactions. Entries 1
and 2 show annulation reactions of relatively acidic dicarbonyl compounds. Entry 3
is an example of use of 4-(trimethylammonio)-2-butanone as a precursor of methyl
vinyl ketone. This compound generates methyl vinyl ketone in situ by -elimination.
The original conditions developed for the Robinson annulation reaction are such
that the ketone enolate composition is under thermodynamic control. This usually
results in the formation of product from the more stable enolate, as in Entry 3.
The C(1) enolate is preferred because of the conjugation with the aromatic ring. For
monosubstituted cyclohexanones, the cyclization usually occurs at the more-substituted
position in hydroxylic solvents. The alternative regiochemistry can be achieved by
using an enamine. Entry 4 is an example. As discussed in Section 1.9, the less-
substituted enamine is favored, so addition occurs at the less-substituted position.
Conditions for kinetic control of enolate formation can be applied to the Robinson
annulation to control the regiochemistry of the reaction. Entries 5 and 6 of Scheme 2.11
are cases in which the reaction is carried out on a preformed enolate. Kinetic

171 E. D. Bergmann, D. Ginsburg, and R. Pappo, Org. React., 10, 179 (1950); J. W. Cornforth and
R. Robinson, J. Chem. Soc., 1855 (1949); R. Gawley, Synthesis, 777 (1976); M. E. Jung, Tetrahedron,
32, 3 (1976); B. P. Mundy, J. Chem. Ed., 50, 110 (1973).
172
C. J. V. Scanio and R. M. Starrett, J. Am. Chem. Soc., 93, 1539 (1971).