Bürgi–Dunitz angle
The Bürgi–Dunitz angle (BD angle) is one of two angles that fully define the geometry of "attack" (approach via collision) of a
Practically speaking, the Bürgi–Dunitz and Flippin–Lodge angles were central to the development of understanding of
Additionally, the stereoelectronic principles that underlie nucleophiles adopting a proscribed range of Bürgi–Dunitz angles may contribute to the conformational stability of proteins[6][7] and are invoked to explain the stability of particular conformations of molecules in one hypothesis of a chemical origin of life.[8]
Definition
In the addition of a nucleophile (Nu) attack to a carbonyl, the BD angle is defined as the Nu-C-O bond angle. The BD angle adopted during an approach by a nucleophile to a trigonal unsaturated electrophile depends primarily on the molecular orbital (MO) shapes and occupancies of the unsaturated carbon center (e.g., carbonyl center), and only secondarily on the molecular orbitals of the nucleophile.[1]
Of the two angles which define the geometry of nucleophilic "attack", the second describes the "offset" of the nucleophile's approach toward one of the two substituents attached to the carbonyl carbon or other electrophilic center, and was named the Flippin–Lodge angle (FL angle) by Clayton Heathcock after his contributing collaborators Lee A. Flippin and Eric P. Lodge.[4]
These angles are generally construed to mean the angle measured or calculated for a given system, and not the historically observed value range for the original Bürgi–Dunitz aminoketones, or an idealized value computed for a particular system (such as hydride addition to formaldehyde, image at left). That is, the BD and FL angles of the hydride-formadehyde system produce a given pair of values, while the angles observed for other systems may vary relative to this simplest of chemical systems.[1][3][9]
Measurement
The original Bürgi-Dunitz measurements were of a series of intramolecular
Hence, Bürgi, Dunitz, and thereafter many others noted that the crystallographic measurements of the aminoketones and the computational estimate for the simplest nucleophile-electrophile system were quite close to a theoretical ideal, the
-
The amine-to-carbonyl n→π* interaction in protopine with an unusually short N···C distance of 2.555 Å and a Bürgi–Dunitz angle of 102°.[10]
In the structure of L-methadone (above, left), note the
Similarly, in the structure of protopine (above, center), note the
Theory
The convergence of observed BD angles can be viewed as arising from the need to maximize overlap between the highest occupied molecular orbital (
In the case of addition to a carbonyl, the HOMO is often a p-type orbital (e.g., on an
Complications
Electrostatic and Van der Waals interactions
To understand cases of real chemical reactions, the HOMO-LUMO-centered view is modified by understanding of further complex, electrophile-specific repulsive and attractive
Linear and rotational dynamics
BD angle theory was developed based on "frozen" interactions in crystals where the impacts of
Constrained environments in enzymes and nanomaterials
Moreover, in constrained reaction environments such as in enzyme and nanomaterial binding sites, early evidence suggests that BD angles for reactivity can be quite distinct, since reactivity concepts assuming orbital overlaps during random collision are not directly applicable.[15][9]
For instance, the BD value determined for
See also
References
- ^ a b c d Fleming, I. (2010) Molecular Orbitals and Organic Chemical Reactions: Reference Edition, John Wiley & Sons, pp. 214–215.
- ^ .
- ^ ISBN 9783527616091]
- ^ a b Heathcock, C.H. (1990) Understanding and controlling diastereofacial selectivity in carbon-carbon bond-forming reactions, Aldrichimica Acta 23(4):94-111, esp. p. 101, see [1], accessed 9 June 2014.
- ^ Gawley, R.E. & Aube, J. 1996, Principles of Asymmetric Synthesis (Tetrahedron Organic Chemistry Series, Vo. 14), pp. 121-130, esp. pp. 127f.
- PMID 20622857.
- S2CID 41838636.
- PMID 20499895.
- ^ a b c Radisky, E.S. & Koshland, D.E. (2002), A clogged gutter mechanism for protease inhibitors, Proc. Natl. Acad. Sci. U.S.A., 99(16):10316-10321, see [2], accessed 28 November 2014.
- .
- ^ Hoggard, P.E. (2004) Angular overlap model parameters, Struct. Bond. 106, 37.
- ^ Burdett, J.K. (1978) A new look at structure and bonding in transition metal complexes, Adv. Inorg. Chem. 21, 113.
- ^ Purcell, K.F. & Kotz, J.C. (1979) Inorganic Chemistry, Philadelphia, PA:Saunders Company.[page needed]
- ^ Lodge, E.P. & Heathcock, C.H. (1987) Steric effects, as well as sigma*-orbital energies, are important in diastereoface differentiation in additions to chiral aldehydes, J. Am. Chem. Soc., 109:3353-3361.
- ^ See for instance, Light, S.H.; Minasov, G.; Duban, M.-E. & Anderson, W.F. (2014) Adherence to Bürgi-Dunitz stereochemical principles requires significant structural rearrangements in Schiff-base formation: Insights from transaldolase complexes, Acta Crystallogr. D 70(Pt 2):544-52, DOI: 10.1107/S1399004713030666, see [3], accessed 10 June 2014.