Reports: UNI152391-UNI1: Stereoselective N-Heterocyclic Carbene (NHC) Catalyzed Oxidopyrylium-Enolate [5+2] Cycloadditions towards Bridged, Polycyclic Ethers
T. Andrew Mitchell, PhD, Illinois State University





Compared to the facile conversion of the aldehydes, conjugate addition of pyranone-ketones 6b,c derived from acetoxypyranone-enones 5b,c was non-spontaneous. Interestingly, upon addition of water (5%), trace lactol 7b was observed (entry 1). Increasing the concentration of water proved to be sufficient to afford the desired lactol 7b (entry 2). Similarly, acetoxypyranone-enone 5c afforded the analogous lactol 7c albeit with slightly decreased conversion (entry 3).
In an effort to extend the scope, we treated acetoxypyranone-enal 2a with a variety of alcohols to afford caged acetal-ethers 7e-l. Utilization of excess methanol (CH3CN:MeOH 95:5) with 3Å molecular sieves to ensure the exclusion of water provided acetal 7e as a single diastereomer in 63% yield (entry 1). Additional functionalized primary alcohols afforded similar results (entries 2-4). More hindered alcohols gave mixed results; isopropanol delivered acetal 7i in moderate yield (entry 5), but tert-amyl alcohol afforded a complex mixture with no acetal 7j detected (entry 6). Although p-cresol gave poor yield, acetal 7k represents an interesting result arising from a different hydroxyl functionality (i.e. phenol) attacking the presumed pyranone-aldehyde 6a (entry 7). Finally, Boc-L-serine methyl ester provided acetal 7l in good yield as an expected mixture of inseparable diastereomers (entry 8).
Entry | ROH | time (h) | 7e-l (% yield) |
1 | MeOH | 6 | 63 (e) |
2 | H2C=CH(CH2)4OH | 6 | 53 (f) |
3 | p-MeO(C6H4)CH2OH | 1 | 62 (g) |
4 | HC≡CCH2OH | 2.5 | 57 (h) |
5 | i-PrOH | 4 | 53 (i) |
6 | 2-methyl-2-butanol | 6 | ND (j) |
7 | p-Me(C6H4)OH | 2.5 | 20 (k) |
8 | Boc-L-serine methyl ester | 1 | 73 (l) |