Hydrophosphinations alkynes

Because organophosphorus compounds are important in the chemical industry and in biology, many methods have been developed for their synthesis [1]. This chapter reviews the formation of phosphorus-carbon (P-C) bonds by the metal-catalyzed addition of phosphorus-hydrogen (P-H) bonds to unsaturated substrates, such as alkenes, alkynes, aldehydes, and imines. Section 5.2 covers reactions of P(lll) substrates (hydrophosphination), and Section 5.3 describes P(V) chemistry (hydrophosphorylation, hydrophosphinylation, hydrophosphonylation). Scheme 5-1 shows some examples of these catalytic reactions. 

Similar to the addition of secondary phosphine-borane complexes to alkynes described in Scheme 6.137, the same hydrophosphination agents can also be added to alkenes under broadly similar reaction conditions, leading to alkylarylphosphines (Scheme 6.138) [274], Again, the expected anti-Markovnikov addition products were obtained exclusively. In some cases, the additions also proceeded at room temperature, but required much longer reaction times (2 days). Treatment of the phosphine-borane complexes with a chiral alkene such as (-)-/ -pinene led to chiral cyclohexene derivatives through a radical-initiated ring-opening mechanism. In related work, Ackerman and coworkers described microwave-assisted Lewis acid-mediated inter-molecular hydroamination reactions of norbornene [275]. 

Recently, intermolecular hydrophosphination of alkynes was also reported with ytterbium-imine complex catalyst precursors [20]. Aromatic alkynes react at room temperature to afford ( )-isomers, while aliphatic ones require heating at 80 °C and, quite surprisingly, (Z)-isomers (trans-addition products) are formed preferentially (Table 4). In this respect the ytterbium-catalyzed reactions are different from the radical process, in which the ( )-isomer formed initially isomerizes to the (Z)-isomer. 

Table 4 Ytterbium-catalyzed intermolecular hydrophosphination of alkynes 1) " YbCHIVIPAle...

A mechanism that involves ytterbium phosphide species has been proposed, similarly to the foregoing intramolecular hydrophosphination. Generation of the phosphide species is supported by the formation of Ph2CDNHPh (after aqueous quench) upon treatment of the imine complex with Ph2PD (Scheme 15). Lanthanide phosphide is known to react with THF, forming a 4-diphenylphosphino-l-butoxyl species [21], which was indeed found as a side product in the catalytic hydrophosphination of disubstituted aliphatic alkynes run in THF, supporting further the ytterbium-phosphide intermediate (Scheme 16). 

The amide [Sm(45a) N(SiMe3)2 ] was a catalyst for an aUene-based hydroamination/ cyclisation. As an illustration, one such product upon hydrogenation yielded a naturally occurring alkaloid. Scheme 4.8. " " The same samarium(lll) amide was also active for the intramolecular hydrophosphination/cyclisation of phosphino-alkenes or -alkynes e.g., H2P(CH2)3C=CPh was transformed into 76. " ... 

Metal complex chemistry, homogeneous catalysis and phosphane chemistry have always been strongly connected, since phosphanes constitute one of the most important families of ligands. The catalytic addition of P(III)-H or P(IV)-H to unsaturated compounds (alkene, alkyne) offers an access to new phosphines with a good control of the regio- and stereoselectivity [98]. Hydrophosphination of terminal nonfunctional alkynes has already been reported with lanthanides [99, 100], or palladium and nickel catalysts [101]. Ruthenium catalysts have made possible the hydrophosphination of functional alkynes, thereby opening the way to the direct synthesis of bidentate ligands (Scheme 8.35) [102]. 

Organolanthanide-catalyzed intermolecular hydrophosphination is a more facile process than intermolecular hydroamination. The reaction of alkynes, dienes, and activated alkenes with diphenylphosphine was achieved utilizing the ytterbium imine complex 9 (Fig. 8) as catalyst [185-188]. Unsymmetric internal alkynes react regioselectively, presumably due to an aryl-directing effect (48) [186]. 

The hydrophosphination of 1,3-butadiene with PH3 catalyzed by Cp2EuH should proceed predominantly via a 1,4-addition and to a lesser extend through a 1,2-addition pathway based on a computational study [189]. The reaction of isoprene with diphenylphosphine indeed forms both regioisomers (49) [186], Isolated double bonds are also reactive, as styrene derivatives are almost as reactive as alkynes (50) however, simple unactivated alkenes, such as 1-decene, are unreactive even at elevated temperatures [186]. 

Metal-catalyzed C-P bond-forming reactions may be divided into two types. In hydrophosphination, a P-H bond is added across a C-X multiple bond (X = C, N, O), as reviewed recently [3-7]. Scheme 1 shows a typical reaction of a terminal alkyne, showing the two possible regiochemical outcomes. Related reactions are defined in terms of the number of O atoms bound to P in the substrate (Scheme 1). Phosphination (cross-coupling) typically involves substitution at sp or sp carbons with removal of the PH group, often by a base (Scheme 1). 

Markovnikov or anti-Markovnikov selectivity in hydrophosphination of alkynes (Scheme 1) depends on the metal catalyst and reaction conditions it is thought to be controlled by the regioselectivity of insertion of an alkyne into an M-H or M-P bond. 

Similar hydrophosphination of alkynes has been used for addition polymerization of diynes, where the regiochemistry could be controlled by the choice of metal catalyst (Scheme 4) [11, 12]. 

Although no mechanism was proposed, the Pd(Me-DuPhos)-catalyzed asymmetric hydrophosphination of an alkyne with a phosphine-borane under kinetic resolution conditions (Scheme 6) presumably involves similar insertion and reductive elimination steps [14]. 

Scheme 11 Proposed mechanism for Pd-catalyzed alkyne hydrophosphination using a diphosphine...

Scheme 12 Pd-catalyzed hydrophosphination of an alkyne using a diphosphine and a silane...

More recently, hydrophosphination of butadiene with PH3 catalyzed by the precursor Cp2EuH was investigated computationally [33]. Consistent with the previous experimental work on aUcene hydrophosphination, the active species was proposed to be the phosphido complex Cp2Eu(PH2), and P-C bond formation occurred by insertion into the Eu-P bond. Hydrophosphination of such conjugated dienes by f-element catalysts does not appear to have been studied in the laboratory, but dienes have been prepared from alkyne hydrophosphination, as described below. 

The complex Ca(PPh2)2(THF)4 catalyzed hydrophosphination of phenyl-substituted alkynes with diphenylphosphine (Scheme 21). The proposed mechanism includes insertion of the alkyne into the Ca-P bond and protonolysis of the new... 

In a simpler example, hydrophosphination oligomerization of the bifunctional substrate 24 was mediated by catalytic -BuLi, presumably by nucleophilic attack of the secondary phosphido anion on the alkyne of another molecule (Scheme 30) [48, 49]. 

Scheme 30 Lithium-catalyzed hydrophosphination/oligomerization of a secondary phosphine/ alkyne...

In ccaitrast, syn-hydrophosphination of alkynes was accomplished using a catalyst obtained by treatment of Co(acac)2 with a mixture of LiPPh2 and PHPh2 (Scheme 32). The nature of the catalyst and mechanism of P-C bond formation were not reported, but the syn stereochemistry is consistent with an insertion step [52]. 

Examples of electrophilic addition of secondary phosphines to alkenes or alkynes were described. [114, 124, 125, 135]. Glueck [124-126] reported enantioselective tandem reaction of alkylated/arylation of primary phosphines catalyzed by platinum complex, proceeding with formation of chiral phosphaace-naphthenes. Palladium-catalyzed hydrophosphination of alkynes 219 tmder kinetic resolution conditions gave access to 1,1-disubstituted vinylphosphine boranes 220. However, despite screening several chiral ligands, temperatures, and solvents, the... 

Join B, Mimeau D, Delacroix O, Gaumont A-C (2006) Pallado-catalysed hydrophosphination of alkynes access to enantioenriched P-stereogenic vinyl phosphine-boranes. J Chem Soc Chem Commun 3249-3251... 

Rosenberg L (2013) Mechanisms of metal-catalyzed hydrophosphination of aUcenes and alkynes. ACS Catal 3 2845-2855... 

Platinum catalysts of the preceding section activate only the nucleophile (a secondary phosphine), which then reacts with the electrophile (an activated alkene). There are, however, interesting examples of lanthanide complexes activating both the nucleophile and the electrophile towards intramolecular diastereoselective hydrophosphination/cyclisations. In 2000 Marks and co-workers found that certain lanthanide complexes catalyse the intramolecular hydrophosphination of alkenes and alkynes (Scheme 6.13). 

Gaumont and co-workers " reported the Pd-catalysed hydrophosphination of terminal alkynes with racemic secondary phosphine boranes. The general reaction is depicted in Scheme 6.17 and is expected in principle to afford two different types of products 42 (a n -Markovnikov addition) and 43 (Markovnikov addition). 

Scheme 6.17 Product distribution in hydrophosphination of terminal alkynes.

The same reaction was performed in the presence of a source of Pd and a bidentate phosphine in toluene at 50 °C. Methylphenylphosphine borane (41a) was reacted with 1-octyne in the presence of palladium acetate (5%) and dppp (10%) for 35 minutes. Interestingly, the Markovnikov product 43a is obtained in 85% yield, with no trace of 42, meaning that in this case the phosphorus attacks the internal carbon of 1-octyne. The same reaction using bdpp (2,4-dw(diphenylphosphino)pentane) and phenylacetylene (39, R = Ph) also yields regioisomer of 43 with 53% yield. Several experiments with diphenylphosphine borane under different reaction conditions (palladium source, temperature, alkyne) showed that the reaction does not occur in the absence of palladium (0) and that hydrophosphination of 1-ethynylcyclohexene (42) undergoes selective hydrophosphination at the triple bond, with the alkeneic bond untouched. 

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