Stereochemistry at phosphorus

D. Cyclic Esters of Phosphorous Acid.—There has been some controversy about the stable stereochemistry at phosphorus in cyclic phosphites and phosphonites this now appears to be resolved by agreement in a series of papers. The stereochemistry of 2-alkoxy-4-methyl-l,3,2-dioxaphosphorins... 

In accord with the current interest in stereochemistry at phosphorus a number of optical studies on phosphonous derivatives have been carried out. Benschop and his group have achieved a partial resolution of alkyl alkylphosphinates (133) by stereospecific inclusion in cycloamyloses. Optical purities in the range 20—80% were obtained. 

The second paper230 investigated the stereochemistry at phosphorus. The pyramidal nature of the phosphorus group was confirmed, with an inversion barrier of ca. 19 kJ mol-1, slightly greater than in PH3. The barriers for inversion in directly-bonded three-co-ordinate atoms is determined principally by the differences in electronegativity of the atoms.231... 

A noteworthy synthetic application for the reaction of J with a,g-unsaturated phosphoryl compounds is represented by the addition involving hitherto unknown (-)-(Sp)-methylphenylvinylphosphine oxide J 2. The resulting tertiary phosphine oxides 13 with saturated carbon chains and known stereochemistry at phosphorus constitute attractive starting materials for the preparation of optically pure phosphines. The organophosphorus substrate 12 was obtained by decarbomenthoxylation of the enantiomeric ester... 

Phosphorus chemistry and biochemistry are enormous topics, and obviously this essay touches on only a few aspects of the subject many other aspects are discussed in detail in this volume by others. This introduction to the symposium is built around the commanding importance of electrostatics in the chemistry and biochemistry of phosphates and phosphites, but that emphasis necessitated omitting a discussion of many other topics. These include, for example, pseudorotation in the hydrolysis of cyclic esters of phosphorus, a fascinating topic to which Edward Dennis and David Gorenstein and others in my laboratory have made significant contributions (28). The brilliant work of Usher, Richardson and Eckstein (29) which (if you will pardon a pun) ushered in the determinations of the stereochemistry at phosphorus in the reactions of phosphate esters, has been omitted, as has the work of Jeremy Knowles (30) and his coworkers, who demonstrated how to use 0 6, 0 7 and 0 8,... 

The PAP-catalyzed reaction occurs with inversion of stereochemistry at phosphorus, supporting the direct phosphoryl transfer from substrate to a metal-coordinated water or hydroxide nucleophile/ Inspection of the active site (Figure 9) reveals two candidates, a monodentate hydroxo/aquo moiety coordinated to the ferric ion, and a bridging hydroxide. Debate surrounds the identity of the nucleophile and of the substrate-binding mode three mechanistic proposals are summarized in Scheme... 

N-Pent-4-enoyl protected nucleosides (see section of DNA synthesis) have been utilised in an /f-phosphonate-mediated assembly of oligomers containing methyl phosphotriester (138) and phosphoramidite (139) linkages - The stereospecific conversion of /f-phosphonates into phosphoramidites upon treatment with butylamine in carbon tetrachloride has been monitored by NMR and found to proceed with inversion of stereochemistry at phosphorus. ... 

The bicyclic compound (14) formed by the reaction of phosphorus trichloride with an amino-diketone <84JA1164> has been shown to be planar, which has been interpreted as evidence for the delocalized dipolar canonical structure (15) rather than the neutral form (14). It forms a silver complex with trigonal bipyramidal stereochemistry at phosphorus <91JA1071>. 

Methods for the detection of changes in stereochemistry at phosphorus were developed over a century after optical methods were utilized for reactions at carbon. Phosphate diesters and monoesters require isotopic... 

Employing the p-diastereomer of ATP(aS) as substrate, Coderre and Gerlt (1980) determined the absolute stereochemistry of the product cAMP(S) to be Rp. This result demonstrates that the enzyme catalyses cyclization with overall inversion of stereochemistry at phosphorus. Confirmation was provided by chiral phosphate analysis, taking advantage of the reversibility of the adenylate-cyclase reaction and employing chiral, dia-stereomerically pure cAMP(a 0) as substrate. The most simple explanation for the observed stereochemistry is a mechanism involving direct intramole-... 

An important new development is the demonstration that Diels-Alder reactions with phospholes and fumaronitriles are greatly accelerated under pressure, and this has led to the synthesis of a number of new 7-phosphanorbornene derivatives. Thus, 3,4-dimethyl-1-phenylphosphole reacted with fumaronitrile at 30 C under 9 kbar for 24 h to give an adduct in 67% yield (Equation (8)) <89T7083>. The stereochemistry at phosphorus was confirmed by x-ray analysis. 

Many of the known phospholene oxides have been reduced to phosphine form, and this constitutes the best method at present for obtaining both 2- and 3-phospholenes. The latter are of special interest when the ring bears 2- or 2,5-substituents with HSiCl3 as the reducing agent (and some others), the stereochemistry at phosphorus in the oxide is preserved, and because of the high barrier to pyramidal inversion characteristic of phosphines there can be stable cw,tra 5-isomers where the tricovalent phosphorus acts as a chiral center (Equation (48)). Examples with several substitution patterns are known. 

The addition of resolved P-chiral hydrogen phosphinates to alkenes has been accomplished without significant loss of the stereochemistry at phosphorus (Scheme 4.84) [124]. This reaction was achieved with the use of a radical initiator. One of the attractive aspects of this chemistry was that it proceeded under solvent-free conditions. The reaction was regioselective for the anti-Markovnikov product, and fair to moderate yields of the alkyl-phosphinate were obtained. Generally, high yields of the alkylphosphinate were obtained for a host of terminal alkenes as well as strained internal alkenes such as norbomene. Internal alkenes were significantly less reactive and satisfactory conversions were only... 

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