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Helix Theory

 

An Electronic Helix Theory for Molecular Chirality and Chiral Interactions

Zhigang’s key scientific contribution has been the development of a new electronic helix theory for molecular chirality and chiral molecular interactions. The theory was originated from his initial thinking on the nature of molecular chirality while an undergraduate at Lanzhou University, China and eventually matured and published while a graduate student with Professor Thomas J. Katz at Columbia University in the city of New York.

While at Columbia he independently published 4 papers on this subject:

(1) Wang, D. Z.* “Conservation of Helical Asymmetry in Chiral Interactions”, Tetrahedron, 2005, 61, 7125-7133. The online supporting material of this paper provides a conceptually new and generally predictive stereochemical rationales to an extensive range of asymmetric catalytic reactions, interested readers may click here PDF.

(2) Wang, D. Z.* “Catalyst-substrate Homohelical Character Matching Determines Enantiomeric Excess”, Tetrahedron, 2005, 61, 7134-7143.

(3) Wang, D. Z.* “Conservation of Helicity and Helical Character Matching in Chiral Interaction”, Chirality, 2005, 17, S177-S182.

(4) Wang, D. Z.* “A Helix Theory for Molecular Chirality and Chiral Interaction”, Mendeleev Communications, 2004, 6, 244-247.

For research highlight: “Conservation of Helical Asymmetry: Electronic Theory for Chiral Interactions Has Powerful Consequences in Asymmetric Catalysis”, Chemical & Engineering News, Sept 29, 2003, 34-35.

An educational tutorial on this theory may be downloaded here:  PDF.

In essence, three things were said:
(a) Chirality = Helicity, they are just the same thing;
(b) Homohelical interactions are electronically favored;
(c) These interactions are most favored when the interacting electronic helices are energetically equal to each other.

The theory agrees well with all the major experiments reported since the birth of asymmetric synthesis in 1960s, accommodates results that conventional steric theories cannot, and promises predictive power. From a conceptually novel scenario, it reveals that effects in stereochemical control conventionally attributed to steric hindrance instead have an electronic basis.

Papers (1-2) present a full account of this theory; paper (3) describes theoretical correlations of this work with known concepts and theories, notably Pearson’s classical Hard and Soft Acid-Base (HSAB) theory, Parr’s electronic polarizability theorem in Density Function Theory (DFT) framework, and Chattaraj’s principle of maximum chemical hardness; paper (4) summaries the major points of the theory and is an invited contribution on the occasion of celebrating the 130th anniversary of Van’t Hoff’s landmark discovery of the carbon tetrahedron geometry.

While the work may appear to be “theoretical” at first sight, it in heart completely focuses on addressing real problems in synthetic organic chemistry, particularly the electronic nature of molecular chirality phenomena and the electronic origin of enantioselection.

Enantioselection, that is, the formation of one enantiomer preferentially over its mirror image in an asymmetric reaction, is usually thought to have a geometrical origin thus to favorably develop through a transition state that has less steric hindrance. It is, therefore, often analyzed by means of steric size-based considerations. However, experimental observations contradicting the prevalent steric theories abound in literature. Moreover, it is fundamentally disturbing that, with this steric scenario, one seems to be always able to explain a stereochemical event only after the experiment, but not to predict it beforehand. Clearly something critical is missing from our fundamental understanding of molecular chirality and chiral interactions.

Exemplified below are five chiral catalysts that all promote asymmetric hydrogenation of 1 under identical conditions and within the same mechanistic framework. All can be geometrically characterized by the same quadrant diagram 2 which in turn predicts that their predominant product enantiomer should all be (S)-3. But surprisingly, they induce dramatically different stereochemical courses. Such intriguing stereochemical phenomena are not accommodated with current steric theories.

 

Interested readers would find that this new theory offers a conceptually novel scenario towards understanding molecular chirality and chiral interactions.

The helix theory shows that complex molecular chiralities can be generalized on the basis of their inherent electronic helicities, being either right- or left-handed; In short, chirality and helicity are just the same thing! In the molecular world, chirality should not simply be regarded as a consequence of the degradation of symmetry as in the macro-scale world; It is the helical electronic identity that distinguishes chiral molecules fundamentally from achiral molecules.

 

It also shows that effects conventionally attributed to steric hindrance might instead have an electronic basis, and that a new electronic effect, which we call homohelical interaction, generally controls the stereochemical course of chiral processes. In essence, the theory says that the underlying principle of chiral interactions is the conservation of molecular electronic helicity, that is, a chiral catalyst will prefer forming the chiral product, or a chiral host will prefer recognizing the chiral guest enantiomer, that allows the catalyst/host to preserve its helicity--or handedness--at the corresponding enantioselection-determining state. An example on Noyori’s asymmetric hydrogenation systems is shown below. 

 

 

The theory further shows that for high enantioselections to be achieved in an asymmetric reaction, the interacting chiral components in the enantioselection-determining state, such as catalyst-substrate, or host-guest, must be helically matched. The work is essentially a chiral version of the classical hard and soft acid-base (HSAB) theory.

 

 

 

The theory has acted as a critical guiding force in our research program on the rational design and discovery of enantioselective catalysis processes. For our recent work in this area, please check PUBLICATION webpage.