Phosphorus-stabilized

This section deals with reactions that correspond to Pathway C, defined earlier (p. 64), that lead to formation of alkenes. The reactions discussed include those of phosphorus-stabilized nucleophiles (Wittig and related reactions), a a-silyl (Peterson reaction) and a-sulfonyl (Julia olefination) with aldehydes and ketones. These important rections can be used to convert a carbonyl group to an alkene by reaction with a carbon nucleophile. In each case, the addition step is followed by an elimination. 

The Wittig and Related Reactions of Phosphorus-Stabilized Carbon Nucleophiles... 

Reviews covering the chemistry of group 2 metal complexes with phosphorus-stabilized carbanions,279 and of molecular clusters of magnesium dimetallated primary phosphanes, are available.2 u Magnesium phosphanes remain rare compounds.281 Lithiation of bromide 98 with BuLi in the presence of tmeda in pentane produces a lithium phosphine dimer subsequent treatment with MgCl2 in EtzO gives the phosphane 99 in 69% overall yield (Equation (19)). The centrosymmetric 99 has Mg-C = 2.217 A Mg-P = 2.77 A (av.).282... 

SECTION 2.4. THE WITTIG AND RELATED REACTIONS OF PHOSPHORUS-STABILIZED CARBON NUCLEOPHILES... 

A limited number of other anionic species have been employed as Michael donors in tandem vicinal difunctionalizations. In a manner similar to sulfur ylides described above, phosphonium ylides can be used as cyclopropanating reagents by means of a conjugate addition-a-intramolecular alkylation sequence. Phosphonium ylides have been used with greater frequency261-263 than sulfur ylides and display little steric sensitivity.264 Phosphorus-stabilized allylic anions can display regiospecific 7-1,4-addition when used as Michael donors.265... 

Alternatively it is possible to have both steps, addition and elimination, occur spontaneously if appropriate reagents are employed. There are two common strategies in use the Wittig reaction and the Wittig-Horner reaction. The Wittig olefination uses a phosphorus-stabilized carbanion (ylid) as a nucleophile and a carbonyl compound as an electrophile. Typically the ylid is generated in situ from a triphenylphosphonium salt and a strong base such as LDA or an alkyl lithium. 

Reviews have featured epoxidation, cyclopropanation, aziridination, olefination, and rearrangement reactions of asymmetric ylides 66 non-phosphorus stabilized carbanions in alkene synthesis 67 phosphorus ylides and related compounds 68 the Wittig reaction 69,70 and [2,3]-Wittig rearrangement of a-phosphonylated sulfonium and ammonium ylides.71 Reactions of carbanions with electrophilic reagents, including alkylation and Wittig-Homer olefination reactions, have been discussed with reference to Hammett per correlations.72... 

The regioselective functionalization of nitrobenzene and benzonitrile derivatives has been performed via nucleophilic aromatic substitution of hydrogen by phosphorus-stabilized carbanions.41 Lithium phosphazenes have been found to be the most suitable nucleophiles for the substitution of hydrogen in nitrobenzene. This method represents a convenient alternative to the vicarious nucleophilic substitution for the synthesis of benzylic phosphorus derivatives using phosphorus-stabilized anions that do not bear a leaving group at the carbanionic centre. 

Although some reactions of electrophilic animation of phosphorus-stabilized anions had already been reported in the literature [5a,d], the first example of such a stereoselective reaction opening access to optically active a-amino phosphonic acids was described in 1992 by Denmark and co-workers [45] and by Jommi and co-workers [46]. Both of these groups used chiral amino alcohols as auxiliaries for diastereo-selective induction in the animating process. Denmark and co-workers chose trisyl azide (2,4,6-triisopropylbenzenesulfonyl azide) as equivalent of NHJ , whereas Jommi and co-workers performed the reaction with DTBAD. 

The phosphorus-stabilized carbanion of 94 was generated at -100 °C with LDA (1.2 equiv.) in THF. Amination reactions were performed both with DTBAD and trisyl azide. Direct addition of a stoichiometric amount of DTBAD (1.1 equiv.) at -100 °C followed by acidic quench led to a mixture of hydrazino products 95 (major diastereomer indicated) in good yield and diastereoselectivity (Scheme 44). 

The phosphorus-stabilized carbanion is an ylide (pronounced ilL-id )—a molecule that bears no overall charge but has a negatively charged carbon atom bonded to a positively charged heteroatom. Phosphorus ylides are prepared from tri-phenylphosphine and alkyl halides in a two-step process. The first step is nucleophilic attack by triphenylphosphine on an unhindered (usually primary) alkyl halide. The product is an alkyltriphenylphosphonium salt. The phosphonium salt is treated with a strong base (usually butyllithium) to abstract a proton from the carbon atom bonded to phosphorus. 

The chemistry of the As=As double bond is quite similar to that of phosphorus. Stabilization of the As=As double bond has been known for almost two decades. The As=As bond distance in bis[tris(trimethylsilyl)methyl]diarsene, (SiMe3)3CAs=AsC(SiMe3)3, prepared by reaction of (MesSOsCAsCb and tert-butyllithium, is typical at 2.45 A. ... 

Electrophilic Azidation of (Chiral) Phosphorus-Stabilized Carbanions. Formation of Optically Active a-Aminophosphonic Acids... 

The successful azide transfer with triisopropylbenzenesulfonyl azide (trisyl azide)2 (see Section 7.1.1.) is also the method of choice for the preparation of optically active a-aminophospho-nic acids from chiral, phosphorus-stabilized carbanions12. 

Once the methods for electrophilic azidation of phosphorus-stabilized carbanions were established a variety of chiral auxiliaries were surveyed to obtain nonraccmic a-aminophosphonic acids. All the compounds tested with the exception of 9 were used in optically active form. (The precursor of 9 was more readily available in racemic form.) The results of electrophilic azidation of these substrates are summarized in Tablet, together with those of ( )-l. Where possible, both methods A and B were tested. 

Table 1. Electrophilic Azidation of Chiral, Phosphorus-Stabilized Anions12...

A high degree of asymmetric induction has been realized in the carbanion-accelerated Claisen rearrangement of phosphorus-stabilized anions. Treatment of 1,3,2-oxazaphosphorinane (166) with freshly prepared lithium dimsylate led to a 95 5 ratio of a-methyl ketones (167) and (168) (Scheme 33). Li coordination combined with steric interactions provide the necessary control elements for stabilization of the highly organized allyl anion conformation (169). 

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