Diphenylphosphino triethylamine

Alkyl- and aryl-pyridazines can be prepared by cross-coupling reactions between chloropyridazines and Grignard reagents in the presence of nickel-phosphine complexes as catalysts. Dichloro[l,2-bis(diphenylphosphino)propane]nickel is used for alkylation and dichloro[l,2-bis(diphenylphosphino)ethane]nickel for arylation (78CPB2550). 3-Alkynyl-pyridazines and their A-oxides are prepared from 3-chloropyridazines and their A-oxides and alkynes using a Pd(PPh3)Cl2-Cu complex and triethylamine (78H(9)1397). 

A palladium-catalyzed protocol for carbon-sulfur bond formation between an aryl triflate and para-methoxybenzylthiol was introduced by Macmillan and Anderson (Scheme 6.66) [138], Using palladium(II) acetate as a palladium source and 2,2 -bis(diphenylphosphino)-l,l -binaphthyl (BINAP) as a ligand, microwave heating of the two starting materials in N,N-dimethylformamide at 150 °C for 20 min in the presence of triethylamine base led to the formation of the desired sulfide in 85% yield. 

The Suzuki coupling reaction is a powerful tool for carbon-carbon bond formation in combinatorial library production.23 Many different reaction conditions and catalyst systems have been reported for the cross-coupling of aryl triflates and aromatic halides with boronic acids in solution. After some experimentation, we found that the Suzuki cleavage of the resin-bound perfluoroalkylsulfonates proceeded smoothly by using [l,l -bis (diphenylphosphino)ferrocene]dichloropalladium(II), triethylamine, and boronic acids in dimethylformamide at 80° within 8 h afforded the desired biaryl compounds in good yields.24 The desired products are easily isolated by a simple two-phase extraction process and purified by preparative TLC to give the biaryl compounds in high purity, as determined by HPLC, GC-MS, and LC-MS analysis. 

A mixture consisting of the Step 2 product (200mg), l,3-bis(diphenylphosphino) propane (8.7 mg), and Pd(OAc)2 (4.7 mg) was placed under a carbon monoxide atmosphere, then treated with 0.2 ml 2-(trimethylsilyl)ethanol, 0.12 ml triethylamine, and 0.9 ml DMSO. The mixture was stirred 3 hours at 70°C and was then extracted with CH2C12. It was washed with 1M HC1, then purified by flash chromatography using EtOAc/petroleum ether, 5 95 to 10 90, and the product isolated in 91% yield, mp = 205°C. 

In 1996, Wermuth reported that various substituted pyridazin-3-yl trifluoromethanesulfonates could be smoothly transformed into the corresponding methyl pyridazin-3-carboxylates (251) using Pd(OAc)2 as palladium source and dppf (l,l -bis(diphenylphosphino)ferrocene) as the ligand for the in situ formed catalyst [95]. A large excess of methanol was used in DMF as the solvent with triethylamine as the base at 50°C. A CO atmosphere was created by simply using a balloon filled with this gas. 

BDA, benzyldimethylamine DABCO, diazabiq clo[2.2.2]octane dcpe, l,2-bis(diq clohexylphosphino)ethane dppf, l,l -bis(diphenylphosphino)ferrocene EDA, ethyldiisopropylamine NEM, N-ethylmorpholine TBACl, tetrabutylammonium chloride TEA, triethylamine TFP, tris(o-furyl)phosphine TOTP, tris(o-tolyl)phosphine. 

Rhodium catalysts have been widely used for C-C bond formation processes [71], Particularly noteworthy are the Rh(I)-catalyzed additions of boronic acids and their derivatives to a.p-unsaturated carbonyl compounds [72-78] and aldehydes [75, 79] (Chapter 4). The groups of Miyaura and Hayashi have shown that Rh(I) catalyzes the addition of sodium tetraphenylborate and arylstannanes to N-sulfonylimines [80-82]. Miyaura and co-workers have also reported the first example of a Rh(I)-cat-alyzed addition of an arylboronic acid to an N-sulfonylimine (77), to give sulfonamide 78 (Equation 13) [83]. Reactions proceeded with 2 equivalents of arylboronic acids using either a cationic Rh(I) catalyst alone, or in combination with appropriate phosphine ligands such as bis(diphenylphosphino)propane or P(i-Pr)3. Boronic esters will also react, particularly in the presence of triethylamine. The reaction does not proceed with simple aldimines, such as PhCH NPh. 

Fig. 1 Reaction scheme for the synthesis of the 2 -0-allyluridine building block Reagents i, l,3-dichlorO l,l,3,3-tetraisopropyldisiloxane in pyridine ii, chlorotri-methylsilane, and triethylamine in 1,2-dichloroethane, iii, 2-mesitylenesulfonyl chloride, triethylamine, and 4-dimethyIaminopyndine in dichloromethane iv, 2,6-dichlorophenol, l,4-diazabicyclo[2 2.2]octane and triethylamine v, p-toluene sulfonic acid monohydrate in THF/dichloromethane, vi, allyl ethyl carbonate, l,4-bis(diphenylphosphino)butane and tris(dibenzylideneacetone)dipalladium(0) in tetrahydrofuran, vii, tetrabutylammonium fluoride in tetrahydrofuran viii, 2-nitro-benzaldoxime and 1,1,3,3-tetramethylguanidine in acetonitrile, ix, 4,4 -dimethoxytrityl chloride and triethylamine in pyridine x, 2-cyanoethoxy M -diisopropyl-aminochlorophosphine and //,iV-diisopropylethyiamine in 1,2-dichloroethane.

Synthesis of 436 To a solution of 434 (175 mg, 0.53 mmol), Pdzdbas (13.7 mg, 0.013 mmol), and l,l -bis(diphenylphosphino) ferrocene (dppf) (30 mg, 0.053 mmol) in A -methylpyrrolidone (9mL) was added triethylamine (150 p,L, 1.06 mmol). The solution was stirred for 30 minutes at room temperature and then warmed to 60°C. tert-Butyl ester 435 (231 mg, 0.74 mmol) in N-methyl-2-pyrrolidone (NMP) (2.5 mL) was added over 1 and V2 hours. The mixture was stirred for an additional 2 hours, cooled at room temperature, and quenched with brine. After extraction with EtOAc, the organic layers were washed with brine and dried over MgS04, and the solvent was evaporated under reduced pressure. Chromatography on silica gel (7/1 pentane/acetone) gave 436 (170 mg, 63% yield) as an inseparable ZIE mixture (80/20). 

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