Enantioselective catalysis of the hetero-Diels-Alder reaction between Brassard's diene and aldehydes by hydrogen-bonding activation: a one-step synthesis of (S)-(+)-dihydrokawain.
The first catalytic enantioselective hetero-Diels-Alder reaction between Brassard's diene and aldehydes has been achieved through hydrogen-bonding activation using TADDOL derivatives as catalysts to afford the corresponding delta-lactone derivatives in moderate-to-good yields and with high enantioselectivities (up to 91 % ee). The reactions can be carried out either under solvent-free conditions or in toluene. On the basis of the absolute configurations of the products and the hydrogen-bonding interaction pattern between TADDOL (alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolan-4,5-dimethanol) and the carbonyl group disclosed by X-ray diffraction analysis, a possible mechanism for the catalytic reaction has been proposed. To demonstrate the usefulness of the methodology, a natural product, (S)-(+)-dihydrokawain, has also been prepared in 50 % isolated yield and with 69 % enantioselectivity in one step starting from 3-phenylpropionaldehyde by using this methodology. Therefore, this catalytic system is one of the most direct approaches to the construction of delta-lactone units, which will make the methodology very attractive for the synthesis of a variety of biologically important compounds and natural products.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.
Haifeng
H
Du
Dongbo
D
Zhao
Kuiling
K
Ding
D000447:Aldehydes / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D004789:Enzyme Activation; D006860:Hydrogen Bonding; D007783:Lactones / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011753:Pyrones / Q000737:chemistry*; D013237:Stereoisomerism; D014297:Trimethylsilyl Compounds / Q000737:chemistry*
D000447:Aldehydes; D000475:Alkenes; C510429:Brassard's diene; D007783:Lactones; D011753:Pyrones; D014297:Trimethylsilyl Compounds; C510430:dihydrokawain