C-P Bond Formations

The phospha-Michael [70] additions are one of the most important methods for 

The first report regarding phospha-Michael additions to enals was made independently and at the same time by the research groups of Melchiorre [71] and 

In 2008, Cordova expanded the scope of the previous reported reaction using different tri- or pentavalent phosphorous nucleophiles [72b]. However, the Michael adducts were formed in low yields and enantioselectivities in the best of the cases. 

Several classes of ligands, such as amino acids (Ll-3, L5), diamines (L9-12), phenanthroUnes (L13-15), and diketone (L18, L20) (or P-keto ester (L19)), have shown remarkable acceleration effects for almost all copper atalyzed UUmarm- 

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Examples of the intermolecular C-P bond formation by means of radical phosphonation and phosphination have been achieved by reaction of aryl halides with trialkyl phosphites and chlorodiphenylphosphine, respectively, in the presence of (TMSlsSiH under standard radical conditions. The phosphonation reaction (Reaction 71) worked well either under UV irradiation at room temperature or in refluxing toluene. The radical phosphina-tion (Reaction 72) required pyridine in boiling benzene for 20 h. Phosphinated products were handled as phosphine sulfides. Scheme 15 shows the reaction mechanism for the phosphination procedure that involves in situ formation of tetraphenylbiphosphine. This approach has also been extended to the phosphination of alkyl halides and sequential radical cyclization/phosphination reaction. ... 

This classical C-P bond-forming reaction (51) has seen limited application in the glyphosate arena, presumably for lack of suitable substrates that can tolerate the vigorous reaction conditions. Typically, C-P bond formation occurs when an alkyl halide reacts with excess neat trialkyl phosphite at temperatures exceeding 100 °C, near the boiling point of the phosphite. An Arbuzov-based strategy for glyphosate requires the synthesis of the... 

The rearrangement has also been extended to P-chiral S-phenyl phos-phinothiolate 79 and 0-phenyl phosphinothioate 80 (Scheme 21). With these asymmetric compounds, the C-P bond formation was found to occur stereose-lectively and with retention of configuration at phosphorus [51]. 

A. Aminophosphonic Acids.— The Michael addition of a dialkyl phosphite to acrylonitrile leads to C—P bond formation and the production in high yield of derivatives of 2-aminoethylphosphonic acid (45). This synthetic method appears to be preferable to those already described. ... 

Chapter 4 C-P bond formation via displacement, addition, or rearrangement... 

The present effort is intended to provide an update of the earlier edition, bringing to the chemist in concise form advances in the approaches to C-P bond formation previously discussed, as well as several other aspects of C-P bond formation. These latter aspects include the generation of organophosphorus compounds from elemental phosphorus (of particular industrial interest for purposes of cost containment) advances in the preparation of phosphoranes, including the use of transient oxophosphoranes as intermediates in organophosphorus compound syntheses and new approaches toward the preparation of compounds with aromatic and vinylic carbon-phosphorus bonds. 

Prior to considering synthetic approaches toward C-P bond formation, we review two areas related to the literature of organophosphorus chemistry that are of particular value to those chemists who do not focus primarily on phosphorus. 

Figure 2.12 Direct aryl-C-P bond formation in a bicyclic compound. 

C-P bond formation using nucleophilic trivalent phosphorus reagents... 

Virtually simultaneously with the development of the Michae-lis-Arbuzov reaction, another closely related approach toward C-P bond formation was introduced. This involved the reaction of the salts of trivalent phosphorus-centered oxyacids with the same haloal-kanes as used in the Michaelis-Arbuzov reaction. First reported by Michaelis and Becker,142 this approach is commonly known as the "Becker reaction" or the "Michaelis-Becker reaction." Fundamental aspects of this reaction system have been reviewed previously.1 2 143... 

A special category of substrate for conjugate addition studies is the substituted cyclopentadieneone series. Numerous reaction conditions have been investigated, leading to a variety of products with new C-P bond formation.434 138 The nature of product formation appears to be very dependent on details of the reaction conditions, and systematic evaluation is required before the reaction can be used for synthetic purposes. 

As in prior chapters, we review historically significant approaches toward C-P bond formation, noting the advantages and disadvantages of classical approaches, contemplate the more recent advances, and consider the opportunities associated with each. Detailed experimental procedures for examples of each of the types of reactions are provided. 

Although these approaches to aromatic C-P bond formation resemble in some ways reactions useful for C-P bond formation in aliphatic systems, clearly there are structural/electronic restrictions and differences in mechanisms. Other approaches to aromatic C-P bond formation are of greater generality and usually more efficient. 

Figure 6.13 Aluminum chloride-mediated C-P bond formation.

The C—P bond formation of sp3 hybridized C—P bonds is readily achievable using the Michaelis-Arbuzov reaction. Such a method is not applicable to form heteroaryl Csp2—P bonds, but Pd-catalyzed reactions provide suitable approaches to such compounds. 

The formation of an s/Z-hybridized C—P bond is readily achievable using the Michaelis-Arbuzov reaction. Such an approach is not applicable to form heteroaryl C—P bonds in which the carbon atoms are sp2 hybridized, whereas palladium catalysis does provide a useful method for Csp2—P bond formation. The first report on Pd-catalyzed C—P bond formation was revealed by Hirao et al. [134-136]. Xu s group further expanded the scope of these reactions [137, 138], They coupled 2-bromothiophene with n-butyl benzenephosphite to form n-butyl arylphosphinate 161 [137]. In addition, the coupling of 2-bromothiophene and an alkylarylphosphinate was also successful [138], For the mechanism, see page 19-21. 

Pd-catalyzed C—P bond formation on the benzene ring of quinoxaline has been reported. Phosphoric acid ester 102 was prepared from 7-bromoquinoxaline 101 and diethylphosphite via a Heck-type reaction [59],... 

Phosphonium salts can be synthesized by the transition-metal-catalyzed addition reaction of triaryphosphines and acids to unsaturated compounds. The reaction of PPh3, CH3SO3H, and alkynes in the presence of a palladium or rhodium catalyst gave alkenylphosphonium salts. Although Pd(PPh3)4 directed the C-P bond formation at the internal carbon atom of aliphatic 1-alkynes (Markovnikov mode), [RhCl(cod)]2... 

The mechanism of this reaction was considered on the basis of hydropalladation (Scheme 14). To minimize steric repulsions, the palladium hydride complex approaches the C=CH2 moiety of the allene in the anti-Markovnikov mode from the opposite side of the substituent. This addition gives a 7t—allyl palladium complex with the (Z)-configuration,18 which is converted to the (Z)-product by C-P bond formation, with regeneration of the Pd(0) catalyst. 

The conjugate addition of phosphorus nucleophiles of various oxidation states and in neutral or metallated form constitutes an efficient and well-known method for C—P bond formation [30]. In the case of phosphanes as nucleophiles especially, the corresponding phosphane-borane adducts have been used in 1,4-additions to Michael acceptors. Following the idea to use a chirally modified phosphorus nucleophile in asymmetric Michael additions to aromatic nitroalkenes, we synthesized the new enantiopure phospite 45 starting from TADDOL (44) with nearly quantitative yield. Due to the C2 symmetry, of the... 

In continuation of our efforts to explore the utility of the SAMP/RAMP hydra-zone methodology, we developed the first asymmetric synthesis of a-phosphino ketones via formation of a carbon-phosphorus bond in the a-position to the carbonyl group [70]. The key step of this asymmetric C—P bond formation is the electrophilic phosphinylation of the ketone SAMP hydrazone 87, giving rise to the borane-adduct of the phosphino hydrazone 88 with excellent diastereoselectiv-ity (de = 95-98%). Since these phosphane-borane adducts are stable with respect to oxidation, the chemoselective cleavage of the chiral auxiliary by ozonolysis leading to the a-phosphino ketones (R)-89 could be accomplished with virtually no racemization. Using RAMP as a chiral auxiliary, the synthesis of the enantiomer (S)-89 was possible (Scheme 1.1.25). 

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