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The nucelophile is represented here as :Nu. The substituents, R and R', attached to the carbon atom of the carbonyl group may be an atom such as hydrogen , alkyl groups such as methyl, ethyl, etc. , or other functional groups such as the O- and N-containing groups of esters and amides. In both panels, a second plane, plane II , is defined that is orthogonal to the first, con-taining the carbon and oxygen atoms of the carbonyl, C=O, and bisecting the R—•—R' angle. A third plane, mutually orthogonal to the first two, plane III , contains only the carbon atom of the carbonyl; it corresponds to the plane of the page in the Newman projection at right. In that projection, the vector pointing from :Nu to the carbon of the carbonyl is mirrored across plane I to make clear that the nucleophile can approach from either above or below this plane. The dotted line from :Nu to plane I indicates the computational process of mathematically projecting the geometric point representing :Nu onto plane I, which is sometimes a necessary maths operation.
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, α B D {\displaystyle \alpha _{BD}} , and the Flippin–Lodge, α F L {\displaystyle \alpha _{FL}} —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 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 areas of synthetic and 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, α B D {\displaystyle \alpha _{BD}} , and later the Flippin–Lodge angle, α F L {\displaystyle \alpha _{FL}} , were developed to describe the approach of the reactive atom of a nucleophile to the reactive atom of an electrophile. The α F L {\displaystyle \alpha _{FL}} 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. The α B D {\displaystyle \alpha _{BD}} is the angle between the approach vector connecting these two atoms and the plane containing the electrophile. Reactions addressed using these angle concepts use nucleophiles ranging from single atoms and polar organic functional groups , to complex chiral catalyst reaction systems and enzyme active sites. 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. Studies of α B D {\displaystyle \alpha _{BD}} and α F L {\displaystyle \alpha _{FL}} can be theoretical, based on calculations, or experimental , 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 , 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 the combined features on the nucleophile and electrophile impact the stereochemistry of reaction outcomes. 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 needed in the construction of complex natural products and drugs.