Electron-deficient phosphines

In the coupling of the allenyl ester 7 with a terminal alkyne, an electron-deficient phosphine (Ph3P) gave the enyne-conjugated ester 8 as the major product, while an electron-rich phosphine (TDMPP or TTMPP) yielded the non-conjugated enyne esters ( )- and (Z)-9[4],... 

Based on the precedent of Van Leeuwen and Roobeek, livinghouse and co-workers screened a variety of electron-deficient phosphine/phosphite ligands for the rhodium-catalyzed [4-1-2] reaction, which provided an alternative catalyst system for the formation of 5,6- and 6,6-ring systems [13]. The most notable of these was the tris-(hexafluoro-2-propyl) phosphite-modified rhodium complex, which was applicable to both carbon- and oxygen-tethered substrates, and also provided the first example of a facial-directed diastereoselective intramolecular rhodium-catalyzed [4-i-2] reaction (Eq. 4). 

From the same substrates, a different reaction took place when the electron-deficient phosphine was replaced by the electron-rich (p-MeOC6Fl4)3P phosphine. In the presence of this slightly modified catalytic system, the recovery of the organic ligand as a lactone was made possible by oxidation of the intermediate cyclic alkoxycarbene with N-hydroxysuccinimide, a mild oxidant which did not destroy the catalyst (Scheme 10.13) [52]. 

Scheme 9. Cycloisomerization of pent-4-yn-l-ols catalyzed by ruthenium catalysts bearing electron deficient phosphine ligands.

The electronic and steric properties of the phosphine ligand(s) can have dramatic effects on the rate and selectivity of the rhodium catalysts. As mentioned above, electron-rich alkylated phosphines generally have a negative effect on the rate and regioselectivity, while more electron deficient phosphines such as PPhs and phosphites (see Electron Deficient Compound) generate more active and regioselective catalysts (Table 3). 

In 2005, Sames and co-workers reported the highly selective (>50 1) C2-arylation of NH-free indoles using a rhodium complex derived from an electron-deficient phosphine as the catalyst, CsOPiv as a base, and iodoar-enes as coupling partners (Scheme 37, 05JA4996). Mechanistic studies revealed that a highly electrophilic Ar-Rh(III) complex was formed in situ through the oxidative addition of aryl iodide to Rh(I) (Scheme 38). Then the displacement of the phosphine ligand by indoles takes place, followed by... 

Although there is no report on rhodium-catalyzed selective Nl-arylation, Sames described a direct C2-arylation of indoles catalyzed by rhodium complexes [216]. When the rhodium catalyst was mixed with an electron-deficient phosphine ligand, a weak base, and an aryl iodide, a highly electrophilic and reactive Ar-Rh(lll) species was generated in situ. The catalyst then promotes the C-H bond activation at the C2 position and arylation would take place selectively at C2 as demonstrated by the transformation of 141 and 142. 

A series of new phosphinooxazoline ligands have been recently prepared and tested in the asymmetric Heck reaction. Synthesis of the ligands involved the aromatic nucleophilic substitution of aryl fluorides with phosphide nucleophile generated from the corresponding phosphine and KHMDS (eq 49). The reaction proceeded in good yields, but proved to be more sluggish with electron-rich aryl fluorides and failed completely when the addition of electron-deficient phosphines was attempted. 

In a related ARCIS process, the Pd-based cross-coupling of o-bromobenzyl alcohols with o-iodobiphenyls under basic conditions (cesium carbonate) with palladium catalysis allows the preparation of several highly substituted triphenylenes. The use of an electron-deficient phosphine ligand is sufficient to assure the formation of two C-C bonds at the expense of a C-C and a C-H bond [71b], Another approach for the synthesis of triphenylenes involves the [2+2+2] trimeiization of benzynes, generated in situ from benzoic acids [71c]. The cooperative Pd(II)/Cu(II) catalytic system was found to be suitable for ortho C-H bond activation in benzoic acids followed by decar-bonylation (Scheme 22.49). 

Yanagisawa, S. Itami, K. Tetrahedron. 2011, 67, 4425 4430. Fagnou has demonstrated a-selective arylation of thiophenes with alternative electron-deficient phosphines. Rene, O. Fagnou, K.Adv. Synth. Catal. 2010,352, 2116-2120. 

Coupling Reactions. Palladium pivalate is an effective catalyst for mild and efficient direct arylation reactions. One account described the intramolecular arylation phenolic ethers (eq 1). Initial optimization with Pd(OAc)2 in conjunction with electron-deficient phosphines led to the desired biphenyl in low yield. Upon the addition of carboxylic acid additives, the yield improved markedly with the optimal additive being pivalic acid. Indeed it was determined that the additive was not needed when Pd(OPiv)2 was errqtloyed as a catalyse although improved yields were observed when the title compound was used in conjunction with the acid additive. The role of the pivalate is believed to be that of a proton shuttle in a concerted metallation-deprotonation (CMD) sequence. A further advantage of using Pd(OPiv)2 was the rate enhancement of the arylation with most reactions complete in less than 6 h (vs. 12 or more hours with Pd(OAc)2). The catalyst was applied to a range of electron-rich and -deficient arenes with good to excellent yields. 

In a review written by Genet and co-workers on electron-deficient phosphines the authors have briefly discussed the relationship between the a-donor ability of a phosphine group and the magnitude of Vpse in the phosphineselenides. As was established by Allen and Taylor some time ago, an increase in this coupling indicates an increase in the ct character of the phosphorus lone-pair orbital (i.e., a less basic phosphine). 

Liu S, Saidi O, Berry N, Ruan J, Pettman A, Thomson N, Xiao J (2009) Electron-deficient phosphines accelerate the Heck reaction of electron-rich olefins in ionic liquids. Lett Org Chem 6 60-64... 

Asymmetric versions of the cyclopropanation reaction of electron-deficient olefins using chirally modified Fischer carbene complexes, prepared by exchange of CO ligands with chiral bisphosphites [21a] or phosphines [21b], have been tested. However, the asymmetric inductions are rather modest [21a] or not quantified (only the observation that the cyclopropane is optically active is reported) [21b]. Much better facial selectivities are reached in the cyclopropanation of enantiopure alkenyl oxazolines with aryl- or alkyl-substituted alkoxy-carbene complexes of chromium [22] (Scheme 5). 

The cross metathesis of acrylic amides [71] and the self metathesis of two-electron-deficient alkenes [72] is possible using the precatalyst 56d. The performance of the three second-generation catalysts 56c,d (Table 3) and 71a (Scheme 16) in a domino RCM/CM of enynes and acrylates was recently compared by Grimaud et al. [73]. Enyne metathesis of 81 in the presence of methyl acrylate gives the desired product 82 only with phosphine-free 71a as a pre-... 

The diamagnetic ylide complexes 34 have been obtained from the reaction of electron-deficient complexes [MoH(SR)3(PMePh2)] and alkynes (HC=CTol for the scheme), via the formal insertion of the latter into the Mo-P bond. The structural data show that 34 corresponds to two different resonance-stabilized ylides forms 34a (a-vinyl form) and 34b (carbene ylide form) (Scheme 17) [73]. Concerning the group 7 recent examples of cis ylide rhenium complexes 36 cis-Me-Re-Me) have been reported from the reaction of the corresponding trans cationic alkyne derivatives 35 with PR" via a nucleophilic attack of this phosphine at the alkyne carbon. 

A related unprecedented double insertion of electron-deficient alkynes has also been reported in the reactions of the linear Pt2Pd heterotrimetallic complex 64 with 65 (RO2CCSCR) (Scheme 24) [95,96]. A series of unsymmetri-cal A-frame clusters 68 has thus been obtained in which a first insertion of the alkyne takes place site-selectively into the Pt-Pd bond vs the Pt-Pt bond (66). After a zwitter-ionic polar activation of the resulting inserted alkene (67), a subsequent reaction with the phosphine unit of the dpmp allows one to obtain the products 68 via the nucleophilic migration of the terminal P atom from the Pd center to the CH terminal carbon (formation of the P-C bond). 

Palladium-catalyzed aromatic C—O bond formation is less developed than palladium-catalyzed aryl amination. Except when the aryl halide is strongly electron deficient,107-110 catalysts ligated by the conventional aryl phosphines such as DPPF and BINAP are ineffective for coupling of... 

The phosphanes useful in this process are built from acyl derivatives of compounds such as those shown in Figure 17.22. During the Staudinger ligation process, once the azide reactant forms the aza-ylide with the phosphine, electrophilic attraction induces the nitrogen to attack the electron deficient carbonyl, which in turn causes release of the phosphonium group and forms the amide bond (Figure 17.23). 

If trivalent phosphoms compounds are to be treated as electron-deficient species, then reactions of oxadiazoles with some Lewis acids should be reported here. 2-Phenyl-l,3,4-oxadiazole reacting with phosphoms trichloride in pyridine solution in the presence of triethylamine at low temperature furnished the respective dichlorophosphine and chlorophosphine, which were trapped by dimethylamine to give the corresponding amides. 2-Phenyl-l,3,4-oxadiazole also interacts over 24 h with the less reactive chlorodiphenylphosphine and dichlorophenylphosphine at room temperature to give phosphines (Scheme 14) <1999CHE1117>. These reactions of oxadiazoles resemble the behavior of 1-alkylimidazoles toward trivalent phosphorus derivatives. 

Some experimental evidences are in agreement with this proposed mechanism. For example, coordinating solvents like diethyl ether show a deactivating effect certainly due to competition with a Lewis base (149). For the same reason, poor reactivity has been observed for the substrates carrying heteroatoms when an aluminum-based Lewis acid is used. Less efficient hydrovinylation of electron-deficient vinylarenes can be explained by their weaker coordination to the nickel hydride 144, hence metal hydride addition to form key intermediate 146. Isomerization of the final product can be catalyzed by metal hydride through sequential addition/elimination, affording the more stable compound. Finally, chelating phosphines inhibit the hydrovinylation reaction. 

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