chosen as the model reaction. Our calculations14 (Figure 2)
on the potential intermediates starting from A suggest that
The atomic radius of Li is smaller than that of Mg, and it
has no vacant coordination site to form similar intermediates.
So 3a (88%) is formed when phenyl lithium reagents are
reacted with isopropenyl acetate at low temperature (Scheme
3).16
Scheme 3
.
Reaction of Isopropenyl Acetate with PhLi under the
Same Conditions As with PhMgBr
Figure 2. Calculations of the relative energy (kcal/mol) in the
reaction of isopropenyl acetate with phenyl magnesium bromide
Grignard reagent.
Acetylacetone (ꢀ-diketone) is produced by isomerization
of isopropenyl acetate under heating (450-500 °C) in the
presence or absence of catalyst.17 From our results, it is
obvious that this isomerization did not take place in the
reaction of isopropenyl acetate with various Grignard re-
agents.
The addition of phenyl magnesium bromide to enol
lactones derived from steroids formed ꢀ-hydroxy ketones by
rearrangement not diols.18 However, to the best of our
knowledge, the application of the rearrangement of isopro-
penyl acetate with Grignard reagents has not been fully
investigated from the synthetic point of view.
In conclusion, compared with other reported methods, this
coupling of isopropenyl acetate with a Grignard reagent
provides a simple and convenient process to symmetrical
1,3-diols. Additional or toxic reagents, such as transition
metal salts, or organotin and related reagents are not required,
and the reaction is carried out under readily accessible
pressure and temperature. Further studies of the scope of
the reaction are in progress.
the stable chair conformation of the six-membered ring of
E is 17.4 kcal/mol lower in energy than A, and that F is 2.3
kcal/mol lower in energy than A. It is expected that E is the
main stable intermediate. After the formation of E, it further
reacts with a Grignard reagent to give the final 1,3-diol
products. Attack by path a leads to the major anti products
of 1, while path b leads to the minor syn products (Scheme
2). This means that the anti product is kinetically favored.
Moreover, the calculation results also show that the anti
isomer 1a lies 1.2 kcal/mol lower in energy than syn isomer
1a. Therefore, the anti product is favorably formed both
kinetically and thermodynamically. The computed structures
and intrinsic reaction coordinates (IRC) of the intermediate
transition states are listed in the Supporting Information. The
results of DFT calculations are in good agreement with those
obtained experimentally (Table 2) and support the reaction
mechanism shown in Scheme 2.15
Acknowledgment. This work was supported by the Nature
Science Foundation of China (Nos. 20772028 and 21072053).
We are grateful to Prof. Qing-Xiang Guo and Dr. Hai-Zhu
Yu from the Department of Chemistry, University of Science
& Technology of China for their helpful discussion.
(14) (a) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin,
K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels,
A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson,
B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03,
revision C.02; Gaussian, Inc.: Wallingford, CT, 2004. (b) Phenylmagnesium
bromide and isopropenyl acetate were chosen as a chemical model. The
DFT method was employed using the B3LYP hybrid functional and the
6-31G(d) basis set. Details are described in the Supporting Information.
(15) (a) Cui, X.; Li, Z.; Tao, C. Z.; Xu, Y.; Li, J.; Liu, L.; Guo, Q. X.
Org. Lett. 2006, 8, 2467. (b) Jiang, B.; Cao, L. J.; Tu, S. J.; Zheng, W. R.;
Yu, H. Z. J. Comb. Chem. 2009, 11, 612.
Supporting Information Available: General methods,
experimental procedures, spectroscopic data, ESI-HR MS of
compounds, crystallographic data of 1a in CIF format, and
computational data. This material is available free of charge
OL102520Y
(16) Al-Aseer, M. A.; Allison, B. D.; Smith, S. G. J. Org. Chem. 1985,
50, 2715.
(17) (a) Hagemeyer, H. J.; Hull, D. C. Ind. Eng. Chem. 1949, 41, 2920.
(b) Morita, M.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2006, 71, 6285.
(18) Zwahlen, K. D.; Horton, W. J.; Fujimoto, G. I. J. Am. Chem. Soc.
1957, 79, 3131.
Org. Lett., Vol. 13, No. 2, 2011
183