The Bürgi–Dunitz angle (BD angle) is one of two angles that fully define the geometry of "attack" (approach via collision) of a nucleophile on a trigonal unsaturated center in a molecule, originally the carbonyl center in an organic ketone, but now extending to aldehyde, ester, and amide carbonyls, and to alkenes (olefins) as well. The angle was named after crystallographers Hans-Beat Bürgi and Jack D. Dunitz, its first senior investigators. Practically speaking, the Bürgi–Dunitz and Flippin–Lodge angles were central to the development of understanding of chiral chemical synthesis, and specifically of the phenomenon of asymmetric induction during nucleophilic attack at hindered carbonyl centers (see the Cram–Felkin–Anh and Nguyen models). Additionally, the stereoelectronic principles that underlie nucleophiles adopting a proscribed range of Bürgi–Dunitz angles may contribute to the conformational stability of proteins and are invoked to explain the stability of particular conformations of molecules in one hypothesis of a chemical origin of life. Definition In the addition of a nucleophile (Nu) attack to a carbonyl, the Bürgi-Dunitz (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. 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 (FL) angle by Clayton Heathcock after his contributing collaborators Lee A. Flippin and Eric P. Lodge. 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. Measurement The original Bürgi-Dunitz measurements were of a series of intramolecular amine-ketone carbonyl interactions, in crystals of compounds bearing both functionalities—e.g., methadone and protopine. These gave a narrow range of BD angle values (105 ± 5°); corresponding computations—molecular orbital calculations of the SCF-LCAO-type—describing the approach of the