Carbanions phosphorus-stabilized

More recent developments are based on the finding, that the d-orbitals of silicon, sulfur, phosphorus and certain transition metals may also stabilize a negative charge on a carbon atom. This is probably caused by a partial transfer of electron density from the carbanion into empty low-energy d-orbitals of the hetero atom ( backbonding ) or by the formation of ylides , in which a positively charged onium centre is adjacent to the carbanion and stabilization occurs by ylene formation. 

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... 

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. 

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. 

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

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. 

In summary, although the azidation of phosphorus-stabilized carbanions at the present time is not yet as stereoselective as azidation, especially of chiral imide enolates (see Section 7.1.1.), the Evans reagents2 also provide a promising methodology for the preparation of optically active a-aminophosphonic acids12. 

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). 

Excluding the a-P-, a-Si-substituted carbanions which are listed in Table 2, there exist relatively few simple a-P-substituted carbanions whose structures are known. References to the crystal structures of some tri (alkyl or aryl) substituted phosphines are listed in Table 4. Few if any of these compounds have been utilized as synthetic reagents. Only two synthetically useful phosphorus-stabilized carbanions of Group la or Ila metal cations have been examined by X-ray diffraction analysis. Hie lithium carbanion of 2-benzyl-2-oxo-l,3,2-diazaphosphorinane (198) crystallizes as a monomeric bis-THF solvate (199) with a tricoordinate lithium atom. The magnesium salt of diethoxyphosphinyl acetone (200) is cluirac-terized as an intramolecularly chelated trimer similar in structure to [Mg(acac)]3. The Cu salt of this 3-keto phosphorus-stabilized anion exists only as a monomer. 

The ready alkylation of sodium phosphonate carbanions with chloro- or bromoacetates in THF provides a useful access to dialkyl 2-(alkoxycarbonyl)ethylphosphonates bearing a variety of alkyl, aryl, cyano, keto, or phosphoryl groups at the cx-carbon (Scheme 8.43). By using a chiral auxiliary, the alkylation of phosphorus-stabilized benzylic carbanions with bromoacetate proceeds with high diastereoselectivity to provide an easy access to optically active alkylphosphonic acids. ... 

Denmark, S.E., and Dorow, R.L., Stereoselective alkylations of chiral, phosphorus-stabilized benzylic carbanions, J. Org. Chem., 55, 5926, 1990. 

Alkenation of carbonyl compounds can be used as a general method for the synthesis of enol ethers. The Homer-Wittig reaction of the phosphorus-stabilized carbanion (8) with aldehydes or ketones gives the adducts (9), which on heating eliminate to give the enol ethers (10) as a mixture of ( )- and (Z)-isomers. Since the two diastereomeric adducts (9) can be separated and the elimination reaction is stereospecific, this method can be used to prepare the individual geometrical isomers of (10) according to Scheme 2. 

In the chemistry of phosphorus-stabilized carbanions the number of publications reporting theoretical studies and those reporting mechanistic studies have increased following the reduction in these numbers last year. One of these reports includes the isolation and separate decomposition of certain oxaphosphetanes and this has allowed the first kinetic study of the second step of the Wittig reaction, albeit for a rather special system. Complex phosphonate carbanions and ylides continue to be widely used in synthesis. The number of reports of the use of the aza-Wittig and related reactions in heterocyclic synthesis remains at a high level, although many of these involve relatively minor modifications of earlier work. 

In phosphorus-stabilized carbanions, interaction of the n orbital on the car-banionic center with the o orbital may increase the barrier to rotation about the C -P bond [37],but this interaction has been demonstrated to block rotation insufficiently in hthiated thiophosphonamides, even at low temperature (Fig. 12). It was also observed that HMPA stabilizes the carbanion in lithiated thiophosphonamides by dissociation of the lithium ion, decreasing the rate of rotation about the C-P bond [38]. 

This chapter will discuss carbanion-like reactions that utilize enolate anions. The acid-base reactions used to form enolate anions will be discussed. Formation of enolate anions from aldehyde, ketones, and esters will lead to substitution reactions, acyl addition reactions, and acyl substitution reactions. Several classical named reactions that arise from these three fundamental reactions of enolate anions are presented. In addition, phosphonium salts wiU be prepared from alkyl halides and converted to ylids, which react with aldehydes or ketones to form alkenes. These ylids are treated as phosphorus-stabilized car-banions in terms of their reactivity. 

In terms of its chemical reactivity, an ylid such as 126 may be viewed as a phosphorus-stabilized carbanion that will undergo acyl addition with an aldehyde or a ketone. When this ylid is mixed with cyclohexanone (80), there are two isolated products. The one that is more interesting to an organic chemist is methylenecyclohexane (129), formed in 52% yield the other is tri-phenylphosphine oxide, 130. It is obvious that 129 is not the expected acyl addition product. Formation of 130 indicates that the carbon atom of the ylid has been transferred to the ketone, but the oxygen atom of the ketone has been transferred to the phosphorous atom. Analysis of the reaction shows that the oxygen atom is lost from the ketone, and the CH2 unit of ylid 126 is transferred to form a new C=C bond (in green in the illustration). What is the mechanism ... 

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