1. FROM α,β-UNSATURATED CARBONYLS TO 2-METHOXYFURANS AND BUTENOLIDES
USING A METAL FREE FORMAL INTERMOLECULAR (4+1)-CYCLOADDITION.
Jean-Philippe Croisetière and Claude Spino*
Département de chimie, Université de Sherbrooke
2500 boulevard de l’Université, Sherbrooke, QC, J1K 2R1, Canada
Introduction
Conclusion
Among cycloadditions, the Diels-Alder reaction is one of the most frequently
encountered. This reaction has found its popularity due to the easy control of up to four
stereocenters. The cheletropic (4+1)-cycloaddition between a carbene and a diene is a
similar reaction, though less utilized because of the high reactivity of the carbene
species. Recently, we designed (4+1)-cycloadditions, using chromium aminocarbenes1,
or free dialkoxy carbenes, which are less harmful for the environment.
Diastereoselective (4+1)-cycloaddition
There are more than 24 000 natural compounds isolated to date that possess either a
furan or a lactone moiety. A retrosynthetic analysis reveals the (4+1)-cycloaddition as a
useful key step towards their syntheses, as shown by the disconnections (shown in
red). Here we present a new methodology to access such compounds, using a metal-
free (4+1)-cycloaddition with dimethoxy carbenes.
Intramolecular version8
Orthoester transformations
Future perspective
We have shown that the intermolecular (4+1)-cycloaddition between carbenes and
α,β-unsaturated carbonyles is possible. Ketones give better yields than most
aldehydes. The furans and the butenolides are effectively obtained in high yields
using three different methods. Overall, this method offers a fast way to access to
orthoesters and furans, as well as butenolides.
Results & Discussion
In our previous work8, we have shown that the intramolecular reaction was possible,
affording high yields. The aldehyde, with quantitative yield, showed the best results.
The ketone derivative was also obtained in high yield but the temperature needed to
be increased to 132°C to achieve 65% yield in the case of the ester (23% in toluene at
111°C).
In the future we plan to make this reaction diastereoselective. Using a chiral
carbene to do the addition would allow control of chirality at the α position. The
auxiliary could also be recycled once removed.
1,2 addition problem
Aldehydes gave low yields in some cases because of polymerisation, which we
believe follows a 1,2-addition of the dialkoxycarbene.
1. Claude Spino et al. Org. Lett., 2015, 17 (5), 1312–1315
2. Rigby, J. H. et al. Tet. Let., 1999, 40(13), 2473-2476.
3. Warkentin, J. Acc. Chem. Res., 2009, 42(1), 205-212
4. Hoffmann, R. W. et al. Chem. Ber., 1977, 110, 3405−3409.
5. Warkentin, J. et al. J. Org. Chem., 1996, 61, 9522−9527.
6. Rigby, J. H. et al. J. Am. Chem. Soc., 1996, 118, 12848−12849.
7. Spino, C.; Legault, C. Y. et al. J. Am. Chem. Soc., 2012, 134(13), 5938-5953
8. Spino, C et al. J. Am. Chem. Soc., 2004, 126 (32), pp 9926–9927
9. Graziano, L.; Lesce, R. et al. J. Heterocyclic Chem., 1986, 23, 553
References and acknowledgement