3 years ago

Stereocontrol through Synergistic Catalysis in the Enantioselective α-Alkenylation of Aldehyde: A Computational Study

Stereocontrol through
Synergistic Catalysis in the
Enantioselective α-Alkenylation of Aldehyde: A Computational
Mahendra Patil
We describe the computational study of an interesting class of reactions involving synergistic action of chiral amine and Cu catalyst. The stereoselectivity-determining step of the enantioselective α-alkenylation of aldehyde has been investigated using the density functional theory methods to gain insight into the origin of the product selectivity. We found that the catalytic activation of reactants in the form of enamine and alkenyl Cu(III) intermediates significantly reduces the activation barrier of the addition step through an improved interaction between these two intermediates at the transition state (referred as enamine and Cu catalyst fragments of the transition state in the text). The transition-state stabilization through interaction between catalytic fragments, as demonstrated by the interaction/distortion model, clearly outperforms destabilization incurred due to the distortion of catalytic fragments and hence is recognized as a major factor contributing to the high stereoselectivity of reaction. Furthermore, the metal–enamine interaction described through the Cu···C7 distance is identified as a vital noncovalent interaction at the transition state. Our calculations show that the catalytic (covalent) activations and metal–enamine interaction can operate in tandem to amplify the net interaction between two catalytic fragments. The cooperative nature of these interactions is also reflected in the trend of interaction energies, which show a large variation with a subtle change in the metal–enamine interaction. Our computational model verified for the different catalytic combinations of chiral amine and Cu catalysts successfully rationalizes the experimentally observed enantioselectivity.

Publisher URL: http://dx.doi.org/10.1021/acs.joc.7b02822

DOI: 10.1021/acs.joc.7b02822

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.