Ligands X-Phos

Migration of alkenyl-Pd(II) intermediates may occur during Heck reaction of enol phosphates, but it may be suppressed by using the X-Phos ligand. ... 

Additional work on alkyl platinum reactions has been completed which mostly supports the generality of these observed insertion reactions. Treichel and Wagner 153) have varied the choice of phosphine ligand utilizing the complexes Pt(phos)2(CH3)X (phos = PEtj, X = Br, I and phos = PPhMe2, X = I) both ionic intermediate and inserted products were obtained. 

Implementation of the C5, C5 -hydroxy lation protocol as described in Scheme 7.19 above (71/72 to 73/74) provided further efficiencies. The C5,C5 -chlorination proceeded uneventfully, but the chloro to alkoxy interchange was difficult and required optimization of the reaction conditions. The catalyst system derived from Pd2dba3 and the X-phos(t-Bu) ligand proved to be effective in the coupling with KOH to provide the desired bisphenol. The resulting product was highly unstable and decomposed under a one-pot alkylation protocol. Isolation of the bisphenol under carefully controlled conditions followed by immediate benzylation (BnBr, NaH, DMF) furnished key intermediate 79 in 70 % yield. 

FIGURE 8. X-phos, a derivative of ligand 11 in Figure 5, synthesized for amination of unactivated aryl tosylates... 

Reaction of diarylamines with aryl nonaflates as part of the synthesis of discrete oligomeric triarylamines has also been reported104. Only one paper reports the palladium-catalyzed reactions of diarylamines with aryl tosylates this reaction was conducted with X-phos 31 (Figure 8) as the ligand in mixed solvents of 5 1 toluene t-butanol98. 

Preparation of the very active catalyst (X-Phos)2Pd from (MeCN)2PdCl2 starts by ligand exchange with TMEDA, which is followed by reaction with MeLi at 0°, and further treatment with X-Phos and 2-(o-chloropheny l)ethylamine, prior to warming to room temperature to split off indoline. The precatalyst (before elimination of indoline) can he used directly for A-arylation of arylamines. 

Barluenga et al. [87] developed a one-pot synthesis for indoles from o-bromoanilines and alkenyl bromides via a cascade alkenyl amination/Mizoroki-Heck reaction. In order to improve the yields of their procedure, they studied the cyclization of preformed imine 113 to indole 114 in the presence of DavePhos and X-Phos as supporting ligands (Scheme 6.30). 

X-Phos is probably the most active and versatile ligand of the biphenyl monophosphines for C—N bond formations [30], It is one of the very few ligands that was found applicable to the conversion of nonfluorinated sulfonic esters [30]. These substrates are very attractive from an economical point of view [30]. 

Recently, Buchwald reported the coupling of aryl nonaflates [154] with soluble bases under microwave irradiation. With a catalytic system comprising Pd2(dba)3, and either XantPhos, X-Phos or an X-Phos derivative as ligand, Buchwald efficiently coupled electron-rich and electron-neutral aryl nonaflates in the presence of DBU or MTBD as base, even when bearing functional groups, such as carbonyl-containing groups [155]. 

Buchwald investigated aminations of aryl tosylates in a detailed study [30]. Among a variety of ligands, X-Phos proved to be superior for a variety of coupling partners, while furthermore a catalyhc system generated from Pd(OAc)2, X-Phos and CS2CO3 in a toluene/t-BuOH solvent mixture allowed for the efficient coupling of benzenesulfonates. In addihon to commonly employed amine nucleophiles, amides could be arylated efihciently. 

However, in their study on the amination of aryl tosylates with X-Phos as ligand and CS2CO3 or NaOt-Bu as base, Skjaerbaek and colleagues obtained low yields. 

Buchwald also reported details of the arylation of malonates using monodentate biaryl phosphine ligands [220], Here, with Pd(OAc)2, t-Bu-DavePhos and the inexpensive base K3PO4 diethyl malonate could be arylated successfully. Later, Buchwald also reported on the arylation of malonates employing the attractive aryl benzene sulfonates [221] when, by using Pd(OAc)2 and X-Phos as the catalytic system, together with CS2CO3 as base in toluene, diethyl malonate could be successfully arylated (Scheme 3.15). 

Use of Non-halide Electrophiles for the Direct Functionalization of Heteroarenes. A palladium-catalyzed direct arylation employing aryl tosylates for the functionalization of various heterocycles was reported (eq 182). Use of an alcoholic cosolvent ( BuOH) and X-Phos as the ligand was key to the success of the transformation. One example with more atom-economical aryl mesylates was also reported, but in a lower yield. Later, more general conditions were developed for arylation with mesylates, employing CM-Phos as the ligand for Pd (eq 183). Other intra-and intermolecular examples with mesylates have recently been reported. ... 

Often catalyzed by a variety of palladium complexes or simply by a mixture of Pd(OAc)2 and PR3, these involve initial reduction of a Pd(II) precursor to Pd(0), normally stabilized by a single 2e ligand, L, typically a phosphine or an NHC. Subsequent oxidative addition of RX generates an R-Pd(II)(L)X intermediate. Basic, bulky phosphines, such as P(t-Bu)3 or X-phos (4.11) facilitate the OA by favoring the formation of this highly reactive zerovalent, 1 1 complex, PdL, in line with the idea that the microscopic reverse, RE from Pd(II), often takes place from a three-coordinate LPd(R)(X)... 

Although electron-rich aryl tosylates are electronically deactivated, the use of monophosphine biphenyl ligand X-Phos in combination with Pd(OAc)2 enables a clean arylation of 1,4-disubstimted triazoles with these electrophiles (Scheme 39)[94]. 

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