Shi Z, Loh T.-P * University of Sciences and Technology of China, Hefei, P. R. of
China and Division of Chemistry and Biological Chemistry, Nanyang Technological University,
Singapore
Organocatalytic Synthesis of Highly Functionalized Pyridines at Room Temperature.
Angew. Chem. Int. Ed. 2013;
52: 8584-8587
Key words
organocatalysis - aza-Rauhut–Currier reaction - Morita–Baylis–Hillman reaction - pyridines
Significance
Reported is the synthesis of 2,3,4,6-tetra- and 2,3,4,5,6-pentasubstituted pyridines
3 and 4 from the reaction of allenoates 1 with 1-aza-1,3-dienes 2 via an aza-Rauhut–Currier/cyclization/desulfonation reaction sequence. The starting
materials 1 and 2 were obtained by following reported protocols as cited in the supporting information.
Although 20% TMEDA in toluene was found to be optimum for the reaction, it also proceeds
with other catalysts (alkyl amines) or solvents (MeCN, CH2Cl2, CHCl3, THF), albeit in lower yields. A variety of highly functionalized pyridines were
obtained in moderate to good yields under optimum conditions (eq. 1). Both electron-donating
and -withdrawing groups containing aryls, as well as heteroaryls (R3) may be used. Highly unstable 1 (R1 = Ph, R2 = H) was tolerated under the reported conditions. One example of a one-pot three-component
reaction was reported to further simplify this protocol (eq. 2). A reaction mechanism
starting with nucleophilic addition of TMEDA to 1 was provided without any experimental evidence.
Comment
While the Morita–Baylis–Hillman (MBH) reaction has emerged as a popular synthetic
methodology for providing highly functionalized compounds, its analogous variant,
i.e., vinylogous MBH [Rauhut–Currier (RC)] reaction is lesser known because of the
low reactivity of substrates and the difficulty in controlling the selectivity of
the cross-coupling reaction (see Review below). A majority of RC reactions utilize
air-sensitive phosphine catalysts, and stable amine-catalyzed RC reactions are uncommon.
The current work is an improvement on previous work as it provides valuable highly
functionalized pyridines by using an inexpensive and air-stable catalyst at ambient
temperature. However, lack of easily available starting materials is a limitation
of this method.
Review
K. Kaur, I. N. N. Namboothiri Chimia 2012, 66, 913–920.
