Carbonyl compounds phosphorus nucleophile addition

The most useful methods for the formation of C-C bonds are based on the addition of C-nucleophiles to carbonyl compounds. Among the many variations of this basic scheme phosphorus ylides, capable of olefinating aldehydes or ketones in a single step, have proven to be exceedingly valuable reagents in organic synthesis. 

A wide range of carbon, nitrogen, and oxygen nucleophiles react with allylic esters in the presence of iridium catalysts to form branched allylic substitution products. The bulk of the recent literature on iridium-catalyzed allylic substitution has focused on catalysts derived from [Ir(COD)Cl]2 and phosphoramidite ligands. These complexes catalyze the formation of enantiomerically enriched allylic amines, allylic ethers, and (3-branched y-8 unsaturated carbonyl compounds. The latest generation and most commonly used of these catalysts (Scheme 1) consists of a cyclometalated iridium-phosphoramidite core chelated by 1,5-cyclooctadiene. A fifth coordination site is occupied in catalyst precursors by an additional -phosphoramidite or ethylene. The phosphoramidite that is used to generate the metalacyclic core typically contains one BlNOLate and one bis-arylethylamino group on phosphorus. 

The most common method for the synthesis of phosphinopeptides is the addition of a nucleophilic, trivalent phosphorus species to a carbon electrophile, including conjugated double bonds, alkylating agents, imines, and carbonyl compounds. By analogy with the phosphite ester additions described above, the nucleophilic form of a phosphinic acid is the trivalent species, generated from the more stable, pentavalent PH derivative by deprotonation or by silylation (cf. Scheme 2). 

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. 

Conversion of Phosphorus- or Sulfur-Stabilized C Nucleophiles with Carbonyl Compounds Addition-induced Condensations... 

Nucleophilic phosphorus(LII) reagents undergo 1,4-addition to ot,P-unsaturated carbonyl compounds (and other substrates susceptible to conjugate addition) to yield the corresponding y-functionalized organophosphorus compounds (e.g. 63).129 The precise course and outcome of the reaction depends upon the nature of the phosphorus nucleophile. 

Keywords Ligand, Ether, Amine, Nucleophilic addition, Organolithium, Grignard reagent, Organozinc, Copper, Phosphorus, Conjugate addition. Alkylation, Phosphine, Activated olefin, P-Substituted carbonyl compound... 

The preparation of species such as a-hydroxyphosphonates has been alluded to only briefly here (see Section 3.5). We would note two direct approaches that are available for the preparation of these materials, both involving nucleophilic addition to carbonyl carbon. One of these is referred to as the Abramov reaction that involves the addition of a fully esterified trivalent phosphorus acid to a carbonyl carbon followed by a dealkylation of the phosphorus ester site. This preparation is quite inefficient when ordinary ester linkages are used, but the use of silyl esters overcomes most of these difficulties and allows facile isolation of the target compounds (equation 30). Note that reaction occurs preferentially at the carbonyl carbon and not by displacement of halogen at carbon. Addition occurs preferentially at carbonyl carbon compared to displacement at a carbon-halogen linkage, and provides product if removal of the ester linkage is facile. 

Katti et al. synthesized polyhydroxyphosphines (Stmctures 1-5) by the nucleophilic addition of PH3 or primary phosphines to formaldehyde or other carbonyl compounds (4). The utility of such ligands in the formation of water-soluble transition metal complexes was evidenced in several cases [5]. It should be noted that besides the phosphorus(III) atom, hydroxy groups also can coordinate with soft transitions metals [3, 6]. 

This reaction was first reported by Pudovik in 1950. It is a base-promoted nucleophilic addition of organophosphorus anion to alkenes or alkynes and is generally known as the Pudovik reaction. Occasionally, it is also referred to as the Pudovik addition. In addition, since Abramov discovered a similar addition reaction of phosphorus compounds to carbonyl compounds at the same time, the addition of organophosphorus compounds to activated unsaturated systems (e.g., alkenes, alkynes, ketones, aldehydes,and... 

Addition of Phosphorus Nucleophiles to Carbonyl Compounds Additions of dialkyl H-phosphonates (the Pudovik reaction) or trialkyl phosphites (the Abramov reaction) to carbonyl compounds constitute a convenient route to a-hydroxyphosphonates (Scheme 47.7). 

The first examples of diastereoselective additions of phosphorus nucleophiles to carbonyl compounds, applied to the synthesis of natural product analogs, involved carbohydrate-derived aldehydes and ketones. The achieved diastereoselectivity depended on the kind of sugar and protective groups used, and for the cyclic ketones usually higher diastereoselectivities were observed. In the aldose... 

During the last two decades, several methods have been developed for an asymmetric catalytic addition of phosphorus nucleophiles to carbonyl compounds. " " These reactions are mostly based on Lewis acid catalysis by metal complexes bearing chiral ligands. By using complexes of La," " Al," and Ti, ° high cc-values and a broad... 

Intermediates such as 224 resulting from the nudeophilic addition of C,H-acidic compounds to allenyl ketones such as 222 do not only yield simple addition products such as 225 by proton transfer (Scheme 7.34) [259]. If the C,H-acidic compound contains at least one carbonyl group, a ring dosure is also possible to give pyran derivatives such as 226. The reaction of a similar allenyl ketone with dimethyl mal-onate, methyl acetoacetate or methyl cyanoacetate leads to a-pyrones by an analogous route however, the yields are low (20-32%) [260], The formation of oxaphos-pholenes 229 from ketones 227 and trivalent phosphorus compounds 228 can similarly be explained by nucleophilic attack at the central carbon atom of the allene followed by a second attack of the oxygen atom of the ketone at the phosphorus atom [261, 262], Treatment of the allenic ester 230 with copper(I) chloride and tributyltin hydride in N-methylpyrrolidone (NMP) affords the cephalosporin derivative 232 [263], The authors postulated a Michael addition of copper(I) hydride to the electron-... 

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