Experimental and theoretical studies on the hydrogen-bond-promoted enantioselective hetero-Diels-Alder reaction of Danishefsky's diene with benzaldehyde.
The enantioselective hetero-Diels-Alder (HDA) reaction of Danishefsky's diene with benzaldehyde has been achieved catalytically by a series of alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL) derivatives through hydrogen-bonding activation, affording 2-phenyl-2,3-dihydro-4H-pyran-4-one after trifluoroacetic acid workup in moderate yield and good enantioselectivity. The alpha,alpha'-aryl substituents in the TADDOL molecules are found to exert a significant impact on both the activity and the enantioselectivity of the catalysis. In combination with the experimental investigations, the mechanism of the present reaction has also been studied theoretically using the ONIOM (B3LYP/6-31G:PM3) method with trans-1,3-dimethoxy-1,3-butadiene as the model for Danishefsky's diene. In agreement with the experimental findings, the calculation results indicate that this TADDOL-catalyzed HDA reaction proceeds via a concerted mechanism through an asynchronous and zwitterionic transition structure (TS). The carbonyl group of benzaldehyde is activated by forming an intermolecular hydrogen bond with one of the hydroxy groups of TADDOL. Meanwhile, the intramolecular hydrogen bond between the two hydroxy groups in TADDOL is found to facilitate the intermolecular hydrogen bonding with benzaldehyde. The sense of asymmetric induction is well-rationalized by the analysis of the relative energies of TADDOL-complexed TSs, while the different stereocontrol capabilities exhibited by TADDOLs in the reaction can be qualitatively established on the basis of the structural features of their corresponding TSs.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.
Xue
X
Zhang
Haifeng
H
Du
Zheng
Z
Wang
Yun-Dong
YD
Wu
Kuiling
K
Ding
D000475:Alkenes / Q000737:chemistry*; D001547:Benzaldehydes / Q000737:chemistry*; D002384:Catalysis; D003500:Cyclization; D004148:Dioxolanes / Q000737:chemistry*; D006860:Hydrogen Bonding; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry; D000432:Methanol / Q000031:analogs & derivatives* / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D013237:Stereoisomerism
D000475:Alkenes; D001547:Benzaldehydes; D004148:Dioxolanes; D007659:Ketones; C516101:alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolane-4,5-dimethanol; D000432:Methanol