Hydrophosphination reactions

In view of excess phosphine being inhibitory in many catalytic reactions, it is surprising that the hydrophosphination reaction is not suppressed by the phosphines formed. In agreement with this, the product phosphine P(CH2CH2CN)3 is reluctant to form tetrakis(phosphine)platinum species, allowing the metal complex to be coordinatively unsaturated. Likewise, the... 

A single report on related hydrophosphination reactions of olefins has also appeared in a review article [69]. 

It is also interesting to note that hydrophosphination reactions can be used to generate fluorous-modified trialkylphosphines in high yields. Hence convenient multigram syntheses of the symmetrically substituted fluorous trialkylphosphines P(CH2CH2Rf)3 (138) by free-radical chain reaction of PH3 to the corresponding alkenes H2C=CH(CH2)m 2Rf have been described.289,290... 

Le Grende and coworkers studied the hydrophosphination reaction of isoprene using bis(trimethylphosphine)titanocene as precatalyst obtaining excellent yields and chemoselectivity to the 1,4-tail-addition. The authors expanded the scope of the reaction to a range of catalysts... 

Hydrophosphination reactions, i.e. reactions where a P H bond is added across a multiple bond (usually of an activated alkene) can proceed uncata-lysed or catalysed by transition metal complexes. With suitable substrates. 

To test the validity of this mechanism, it was reasoned that a weak add (t-BuOH or water) should quench the zwitterion 21 and suppress or at least decrease the formation of by-products. This is indeed the case, although the addition of more alkene increases the quantity of by-products, even in the presence of t-BuOH. It should be noted that the presence of these protic additives is not innocent, since it also increases the reaction rates and affects the enantioselectivity. For example adding 20 equivalents of t-BuOH to the reaction of PH(Is)Me with tert-butyl acrylate halves the time for the completion of the reaction (from 5 to 2 days) and doubles the enantiomeric excess from 28% to 56%. The latter enantioselectivity is the best obtained to date with the systems discussed in this section. More evidence for the Michael addition mechanism came from trapping intermediate 21 with electrophiles other than a proton. Scheme 6.12 shows that performing the hydrophosphination reaction in the presence of benzaldehyde produced some of the three-component coupling product 25. 

Organolanthanide complexes differ from late d-block transition metal complexes in several aspects. They are electrophilic, kinetically labile and lack conventional oxidative addition/reductive elimination pathways in their reactions. They have alternative mechanisms to perform catalytic transformations and are being increasingly used in homogeneous catalysis. The hydrophosphination reaction was proposed to proceed through the cycle depicted in... 

In addition, Cordova et al. have developed highly enantioselective organocatalytic hydrophosphination reactions of a,p-unsaturated aldehydes. These novel reactions were catalysed by protected chiral diarylprolinol derivatives... 

The addition of primary and secondary phosphines to alkenes is an atom-efficient approach to the formation of P—C(sp ) bonds. Classically, this reaction has been promoted by radical initiators, bases, and metal catalysts. These approaches have been summarized in several reviews [37 4]. When activated alkenes such as acrylates are used as substrates, the reactions are typically referred to asphospha-Michoel additions. Reactions that promote the addition to unactivated alkenes such has hexane are described as hydrophosphination reactions. The majority of the reactions that have been reported target the formation of neutral phosphines due to their value as ligands for transition metals. In addition, a range of addition reactions between tertiary phosphines and Michael acceptors leading to the formation of phosphonium salts has also been reported. The following sections will highlight representative reactions and example preparations of each class of reactions. 

The preparation of 1,2-bisphosphines bearing electron-withdrawing substituents was accomphshed using a base-assisted hydrophosphination reaction (Scheme 4.13) [16], While the yield of the reaction was moderate (52%), the strength of this reaction was the elimination of the normal requirement for the use of hazardous reagents such as Li[3,5-C HjfCFj) ] to generate the electron-deficient bisphosphine. 

While the majority of hydrophosphination reactions were carried out in organic solvents, a copper-catalyzed hydrophosphination reaction was developed that could be carried out using pure water as the solvent (Schane 4.22 and Example 4.19) [65]. The key to this chemistry was the addition of a surfactant to promote the formation of micelles. Once formed, the reaction was proposed to occur within the core of these aggregates. A considerable amount of substrate-specific reactivity was observed with this system with the highest yields obtained using electron-deficient substrates. 

SCHEME 4.27 Use of a P-stereogenic PCP pincer ligand in asymmetric hydrophosphination reactions [20]. 

While the majority of the hydrophosphination reactions described previously led to the formation of products with almost complete anti-Markovnikov selectivity, devising an approach for the selective formation of the addition product with Markovnikov selectivity can be challenging [79]. To address this deficiency, Gaumont determined that a simple change to the catalyst structure switched the selectivity of the reaction (Scheme 4.29 and Example 4.23) [80]. The key observation was that using ferrous chloride as... 

Need a green or sustainable version of the hydrophosphination reaction for the synthesis of an alkylphosphine... 

Calcium-based catalysts have also shown promise in hydrophosphination reactions (Scheme 4.299) [62]. Treatment of phenylacetylene with diphenylphosphine in the presence of a p-diketiminate-ligated calcium complex afforded an excellent yield of the vinylphosphine. Furthermore, the reaction was highly selective for the formation of the F-stereoisomer. This chemistry provided a transition metal-free route to the synthesis of these valuable targets. 

SCHEME 4.301 Using calcium and ytterbium compounds as catalysts for hydrophosphination reactions [468]. 

When used in hydrophosphination reactions where air-sensitive secondary phosphines are employed, they afford simultaneous protection and assistance in deprotonation of these species by coordination and subsequent activation of the P-H bond, thus priming them for the subsequent attack on C=C centers. 

One of the first functionalized substrates subjected to the asymmetric P-H addition promoted by metal complexes were phosphine-functionalized alkenols, viz., 3-diphenylphosphinobut-3-en-l-ol and 2-diphenylphosphinoprop-2-en-l-ol (Scheme 7) [54]. The target was the diphosphine ProPhos which had previously been prepared by tedious organic manipulations extending to 14 steps from a chiral pool consisting of malic and L-ascorbic acid [55, 56]. The hydrophosphination reaction employing (/ )- was carried out as shown in scheme 7 and showed excellent selectivity in the case of 3-diphenylphosphinobut-3-en-l-ol (four isomeric products in the ratio 2 18 1 4) and moderate selectivity in the case of 2-diphenyl-phosphino prop-2-en-l-ol (1 2 5 8). Isomer 12a was the major product in the case of 3-diphenylphosphinobut-3-en-l-ol (n = 1), and for 2-diphenylphosphinoprop-2-en-l-ol (n = 2), 11a and 11b co-crystallized out. The two analogous substrates gave products that differ in the chirality at the newly formed carbon center. 

The asymmetric hydrophosphination of the cyano-functionalized phosphine has also been undertaken in view of the potential for further manipulation of the cyano moiety to formyl and hydroxyl functionalities [58]. This will serve as an elegant method for accessing these functionalized diphosphines. The diastereoselective hydrophosphination reactions of the c -cyano-functionalized phosphine complex ( = 1) gave the chiral l,2-bis(diphosphino)ethane products in high yield (90%) and stereoselectivity S isomer formed exclusively). For the trans analogue, the absolute stereoselectivity was 10 1 with the S isomer being the major product. 

The generation of a phosphine-functionalized substrate and its coordination to the chiral metal template in order to activate the unsaturated C=C bond toward nucleophilic attack is a prerequisite for the hydrophosphination reactions seen in previous sections. However, in the case of activated alkynes such as dimethyl acetylenedicarboxylate or its diketone analogue, this pre-preparation of the phosphinoalkene is not necessary, and a direct hydrophosphination using two equivalents of diphenylphosphine in the presence of trace amounts of base was found to promote the two-stage hydrophosphination in a one-pot process with diastereoselectivity of 6 1 and in quantitative yield (Scheme 15) [73],... 

When a carboxylate or ketone-substituted alkyne was used for the hydrophosphination reaction, the corresponding monophosphine-substituted intermediate exists as a classical enol-keto equilibrium mixture, which is sensitive to the pH of the reaction. Therefore, by regulating the amount of triethylamine as a noncoordinating external base, the (1,1)- and (1,2)-addition pathways could be... 

The presence of ester or keto functional group is a critical factor, and nonconju-gated aUenes tested did not undergo this hydrophosphination reaction under the same conditions. The amount of triethylamine in this instance was also found to have an impact on selectivity with 10% of amine (based on diphenylphosphine) being the optimum for achieving the desired regio- and stereoselectivity. 

In summary, asymmetric P-H additions leading to the direct enantioselective/ diastereoselective formation of optically pure mono- and polydentate tertiary phosphines are thus a field that has more room for development. This is true especially in the realm of catalytic P-H additions as illustrated in the preceding sections wherein design of better catalysts is currently attracting much attention. It is thus foreseeable that in the near future even more types of enantiomericaUy pure tertiary phosphines with a large range of functionality will be soon available via the asymmetric hydrophosphination reaction. 

Scheme 8.54 Mechanistic difference in the hydrophosphination reactions using Pd(0)/Ni(0) or PdX2/NiX2 species as catalyst precursors...

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