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NHC organocatalytic formal LUMO activation of α,β-unsaturated esters for reaction with enamides.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Cheng, Jiajia Huang, Zhijian Chi, Yonggui Robin |
| Copyright Year | 2013 |
| Abstract | a,b-Unsaturated carbonyl compounds are basic building blocks in organic synthesis. Lewis acid catalysts bearing chiral ligands have traditionally been used for the asymmetric catalytic activation of this class of molecules as Michael acceptors. 2] Indeed, Lewis acid catalysis continues to be a powerful approach in which innovative solutions are still emerging. Representative examples of chiral Lewis acid catalysts include the metal–bisoxazoline complexes introduced by the research groups of Evans and Corey, the multimetallic bifunctional catalysts developed by Shibasaki and co-workers, the bifunctional Lewis acid/base catalysts described by Lectka and co-workers, and the metal–N,N’dioxide catalysts developed by Feng and co-workers. In another direction, organocatalytic methods have received intense attention in the last decade or so. By iminium catalysis, pioneered by MacMillan and co-workers, a,bunsaturated aldehydes and ketones can be activated as electrophiles for a set of highly enantioselective reactions (Scheme 1a). The related equally useful ester substrates, on the other hand, are outside the scope of iminium/enamine catalysis, which has proved to be versatile for aldehyde and ketone substrates. We are interested in the organocatalytic activation of readily available esters for asymmetric synthesis. N-Heterocyclic carbenes (NHCs, typically imidazolium-based NHCs) have been studied previously for the catalysis of transesterification reactions (Scheme 1b). Two mechanisms were proposed for NHC-catalyzed transesterification; one involves ester activation, and the other involves alcohol activation, in which NHC behaves as a base catalyst. Recently, we disclosed the HOMO activation of saturated a-aryl acetic esters through catalysis with NHCs to generate enolate intermediates for enantioselective reactions. Herein we report the formal LUMO activation of a,b-unsaturated esters by NHC catalysis for highly enantioselective reactions with enamides (Scheme 1c). The key step involves the addition of the NHC catalyst to the ester substrate I to form an a,b-unsaturated acyl azolium intermediate II. Unsaturated acyl azolium intermediates of this type were previously generated from enals, a-hydroxyenones, a-bromoenals, ynals, and a,b-unsaturated acid fluorides by (oxidative) NHC catalysis. Lupton and co-workers reported an NHC-catalyzed enol ester rearrangement, which was proposed to proceed by addition of the NHC to the carbonyl group of the ester, followed by Claisen rearrangement. They suggested that an a,b-unsaturated acyl azolium intermediate (such as II) was unlikely to be involved as a key intermediate (Scheme 1b). In a related approach, Smith and co-workers recently reported the use of anhydrides as a,b-unsaturated acyl ammonium precursors with isothiourea catalysts. Each of these elegant methods has its own merits and limitations. For example, with a,b-unsaturated aldehyde substrates, relatively expensive organic oxidants 19] need to be used in the asymmetric oxidative NHC catalysis. The use of ynals as substrates is constrained by the limited substitution patterns (e.g. disubstitution at the a and b carbon atoms is not possible) and somewhat high cost of the ynal compounds. In our approach, the ester substrates are readily available, inexpensive, and stable (easy to handle). Various Scheme 1. a,b) Previously reported related approaches for the activation of carbonyl substrates with organocatalysts. c) LUMO activation of a,b-unsaturated carbonyl compounds by NHC catalysis. Ts = p-toluenesulfonyl. |
| Starting Page | 317 |
| Ending Page | 319 |
| Page Count | 3 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.ntu.edu.sg/home/robinchi/publication%20lists/37%20pdf.pdf |
| PubMed reference number | 23843139v1 |
| Alternate Webpage(s) | https://doi.org/10.1002/anie.201303247 |
| DOI | 10.1002/anie.201303247 |
| Journal | Angewandte Chemie |
| Volume Number | 52 |
| Issue Number | 33 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acetaldehyde Acetic Acid Aldehydes Anhydrides Betaine-aldehyde dehydrogenase Bridged Bicyclo Compounds, Heterocyclic Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone Carnitine esters/Creatinine:MRto:Pt:Urine:Qn Carnitine esters/Creatinine:SRto:Pt:Urine:Qn Catalysis DNA Sequence Rearrangement Esters Ethanol Evan's coding system Fluorides HMGN4 protein, human Ketone Measurement Ketones Ligands Maxillary right third molar abutment NG-Nitroarginine Methyl Ester National Health Care Survey (NHCS) Neonatal hemochromatosis Organic Synthesis Oxidants Solutions Thioctic Acid Thiourea Zinc benzochlorin iminium salt acyl-CoA dehydrogenase acyl-CoA oxidase carbene carbonyl compound enol |
| Content Type | Text |
| Resource Type | Article |
