Diastereotopic, defined

The general subject of asymmetric synthesis has been reviewed extensively (1-5). The term asymmetric synthesis has been defined in more than one way (1,4) however, a useful definition is the one given by Morrison and Mosher (1) a process which converts a prochiral unit [refs. 6 and 7] into a chiral unit so that unequal amounts of stereoisomeric products result. The stereoisomeric products may be enantiomeric or they may be diastereomeric. The substrate molecule must contain either enantiotopic or diastereotopic groups or faces (8,9), since the attack of a reagent at equivalent groups or faces cannot lead to isomeric products. 

In retrospect, it seems unfortunate that in 1971 Morrison and Mosher8 generalized the definition, while keeping the term, an asymmetric synthesis is a reaction in which an achiral unit in an ensemble of substrate molecules is converted by a reactant into a chiral unit in such a manner that the stereoisomeric products arc produced in unequal amounts ( Footnote The substrate molecule must have either enantiotopic or diastereotopic groups or faces) . Obviously the phrase "an achiral unit in an ensemble of substrate molecules is too inexact and requires a great deal of additional explanation, which was partially given by the footnote (note that molecule, i.e., singular, was used ). Currently, the Morrison-Mosher term appears to be equivalent to stereoselective reaction. Unfortunately, this term was only defined in the modem sense by Izumi in 1971, i.e., in the same year the Morrison-Mosher definition was published. 

SUylenes with two different substituents, R R Si, are prochiral, and insertion into an alcoholic RO-H bond should create chirality on the silicon. In particular, if one of the two substituents is chiral, a diastereotopic face can be defined and diastereoselective addition can be expected. Quite recently, the first example of diastreoselective addition of alcohol to diastereotopic silylene has been reported. ... 

Theoretically, four isomeric products can be expected upon addition reactions to the a,/ -unsat-urated nitrile 32 due to the chirality of C-2 and C-3 in the adducts. The simplicity of the product formation, however, reveals a considerable difference in the asymmetric environment between the diastereotopic a- and /J-alkene faces of 32 owing to the defined stereochemical configurations of C-T and C-4 84. Spectroscopic characterizations have established (vide infra) that the stereochemical course of the nucleophilic attack at C-2 is always from the sterically and electronically less demanding a-face of the pentenofuranosyl ring. The configuration of C-3 [cyano up (trans) or cyano down" (c/.r)] was assessed by H- and IJC-NMR spectroscopy84. 

To determine the stereoselectivity of diastereotopic proton abstraction from the Pro-R methylene group of ACPC (9) in the fragmentation (occurring between Pro-S p-C and a-C), 2-ethyl-[3-Di]-ACPC (8a) was prepared with the ethyl side chain and deuterium substituent in cis relationship. Incubation of this compound followed by in situ reductive enzymatic trapping with (25)-lactate dehydrogenase yielded 2-hydroxy-[3-D]-hexanoate where the R,5-placement of D was analyzed by NMR and the D-content by mass spectrometry. These results had defined the stereoselectivity for )5-H-abstraction from the Pro-R methylene of 2-ethyl-ACPC (8) as the proton removal in the overall fragmentation process and by analogy the same in ACPC (9). These results place stereochemical constraints on the ACPC deaminase process and were accommodated in Scheme 10. 

Group-selective hydroalumination in which aluminum hydrides discriminate between diastereotopic alkynes provides access to a class of stereo-defined tertiary alcohols with potential ulilily in natural product synthesis [175]. Among the hydride reagents tested, BuLi-DIBAL or HSul.i-DIBAL enabled superior discrimination to give sp -sp -sp-attached alcohol 145 with extremely high diastereoselectivity (>99% de) (Scheme 6.136). 

Reaction of bis(2,3-dihydroxyphenyl)methane H4L 56 with [TiO(acac)2] and Li2C03 affords a well-defined product (Scheme 7). The diastereotopic behavior of... 

The coordination structures of enzyme-bound manganese nucleotides can in favorable cases be determined by analysis of electron paramagnetic resonance (EPR) spectra of Mn(II) coordinated to O-labeled nucleotides. When the nucleotide is stereospecifically labeled with O at one diastereotopic position of a prochiral center, either oxygen can in principle be bound to Mn(II) in the coordination complex in an enzymic site. When the coordination bond is between Mn(II) and O, the EPR signals for Mn(II) are broadened and attenuated, owing to unresolved superhyperfine coupling between the nucleus of 0 and the unpaired electrons of Mn(II) (23). No such effect is possible with 0, which has no nuclear spin. The effect is observable in samples in which all the Mn(Il) is specifically bound in one or two defined complexes of the nucleotide with the enzyme. Thus the complex Mg(Sp)-[a- 0]ADP bound at the active site of ere-... 

The terms enantiotopic , diastereotopic , and stereoheterotopic should be abandoned to support the pro-Rlpro-S system, just as the terms enantiomeric , diastereomeric , and stereogenic for supporting R -stereodescriptors of the CIP system should be abandoned. In particular, the term enantiotopic will be used only to explain geometric aspects apart from the pro-Rlpro-S system, while the newly-defined term R5-diastereotopic will be used to support the pro-Rlpro-S system. On a similar line, the term enantiomeric will be used only to... 

---