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The Flippin–Lodge angle is one of two angles used by organic and biological chemists studying the relationship between a molecule's chemical structure and ways that it reacts, for reactions involving "attack" of an electron-rich reacting species, the nucleophile, on an electron-poor reacting species, the electrophile. Specifically, the angles—the Bürgi–Dunitz, , and the Flippin–Lodge, —describe the "trajectory" or "angle of attack" of the nucleophile as it approaches the electrophile, in particular when the latter is planar in shape. This is called a nucleophilic addition reaction and it is plays a central role in the biological chemistry taking place in many biosyntheses in nature, and is a central "tool" in the reaction toolkit of modern organic chemistry, e.g., to construct new molecules such as pharmaceuticals. Theory and use of these angles falls into the area of physical organic chemistry, which deals with chemical structure and reaction mechanism, and within a sub-specialty called ''structure correlation''. Because chemical reactions take place in three dimensions, their quantitative description is, in part, a geometry problem. Two angles, first the Bürgi–Dunitz angle, , and later the Flippin–Lodge angle, , were developed to describe the approach of the reactive atom of a nucleophile (a point off of a plane) to the reactive atom of an electrophile (a point on a plane). The is an angle that estimates the displacement of the nucleophile, at its elevation, toward or away from the particular R and R' substituents attached to the electrophilic atom (see image). The is the angle between the approach vector connecting these two atoms and the plane containing the electrophile (see that article). Reactions addressed using these angle concepts use nucleophiles ranging from single atoms and polar organic functional groups to chiral catalyst reaction systems, to complex enzyme active site. These nucleophiles can be paired with an array of planar electrophiles: aldehydes and ketones, carboxylic acid-derivatives, and the carbon-carbon double bonds of alkenes (olefins). Studies of and can be theoretical, based on calculations, or experimental (either quantitative, based on X-ray crystallography, or inferred and semiquantitative, rationalizing results of particular chemical reactions), or a combination of these. The most prominent application and impact of the Flippin-Lodge angle has been in the area of chemistry where it was originally defined: in practical synthetic studies of the outcome of carbon-carbon bond-forming reactions in solution. An important example is the aldol reaction, e.g., addition of ketone-derived nucleophiles (enols, enolates), to electrophilic aldehydes that have attached groups varying in size and polarity. Of particular interest, given the three-dimensional nature of the concept, is understanding how features on the nucleophile and electrophile impact the stereochemistry of reaction outcomes (i.e., the "handedness" of new chiral centers created by a reaction). Studies invoking Flippin-Lodge angles in synthetic chemistry have improved the ability of chemists to predict outcomes of known reactions, and to design better reactions to produce particular stereoisomers (enantiomers and diastereomers) needed in the construction of complex natural products and drugs. ==Technical introduction== The Flippin–Lodge (FL) angle, is the latter-derived of two angles that fully define the geometry of "attack" (approach via collision) of a nucleophile on an trigonal unsaturated center of an electrophilic molecule. Nucleophiles in this addition reaction may range from single atoms (hydride, chloride), to polar organic functional groups (amines, alcohols), to complex systems (nucleophilic enolates with chiral catalysts, amino acid side chains in enzyme active sites; see below). Planar electrophiles include aldehydes and ketones, carboxylic acid-derivatives such as esters, and amides, and the carbon-carbon double bonds of particular alkenes (olefins).〔Ian Fleming (2010) Molecular Orbitals and Organic Chemical Reactions: Student Edition, John Wiley and Sons, pp. 158-160; see also Ian Fleming (2010) Molecular Orbitals and Organic Chemical Reactions: Reference Edition, John Wiley and Sons, pp. 214–215, ISBN 0470746580, (), accessed 5 January 2014.〕〔 In the example of nucleophilic attack at a carbonyl, is a measure of the "offset" of the nucleophile's approach to the electrophile, toward one or the other of the two substituents attached to the carbonyl carbon.〔〔〔 The relative values of angles for pairs of reactions can be inferred and semiquantitative, based on rationalizations of the products of the reactions; alternatively, as noted in the figure, values may be formally derived from crystallographic coordinates by geometric calculations, or graphically, e.g., after projection of Nu onto the carbonyl plane and measuring the angle supplementary to ''L''Nu'-C-O (where Nu' is the projected atom). This often overlooked angle of the nucleophile's trajectory was named the Flippin-Lodge angle by Clayton H. Heathcock after his contributing collaborators Lee A. Flippin and Eric P. Lodge.〔〔E.P. Lodge & C.H. Heathcock (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.〕〔L.A. Flippin & C.H. Heathcock (1983) Acyclic stereoselection. 16. High diastereofacial selectivity in Lewis acid mediated additions of enolsilanes to chiral aldehydes, J. Am. Chem. Soc. 105:1667-1668.〕〔 The second angle defining the geometry, the more well known Bürgi–Dunitz angle, , describes the Nu-C-O bond angle and was named after crystallographers Hans-Beat Bürgi and Jack D. Dunitz, its first senior investigators (see related article). The Flippin-Lodge angle has been abbreviated variously by the symbols φ, ψ, θx, and or ;〔〔R.E. Gawley & J. Aube (1996) Principles of Asymmetric Synthesis (Tetrahedron Organic Chemistry Series, Vo. 14), New York:Pergamon, pp. 121-130, esp. pp. 127f, ISBN 0080418759.〕〔E.S. Radisky & D.E. Koshland (2002), A clogged gutter mechanism for protease inhibitors, Proc. Natl. Acad. Sci. USA, 99(16):10316-10321.〕〔〔A.M.P. Koskinen (2012) Asymmetric Synthesis of Natural Products, Chichester, UK:John Wiley and Sons, pp. 3-7f.〕 the latter pair to closely associate the Flippin-Lodge angle with its sister angle, the Bürgi–Dunitz, or , and will be used here. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Flippin–Lodge angle」の詳細全文を読む スポンサード リンク
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