Aryl iodides amination

The carbonyiation of o-diiodobenzene with a primary amine affords the phthalimide 501 [355,356]. Carbonyiation of iodobenzene in the presence of (9-diaminobenzene (502) and DBU or 2,6-lutidine affords 2-phenylbenzimida-zole (503)[357, The carbonyiation of aryl iodides in the presence of pentaflnor-oaniline affords 2-arylbenzoxazoles directly, 2-Arylbenzoxazole is prepared indirectly by the carbonyiation of (9-aminophenol[358j. The optically active aryl or alkenyl oxazolinc 505 is prepared by the carbonyiation of the aryl or enol triflates in the presence of the opticaly active amino alcohol 504, followed by treatment with thionyl chloride[359]. 

The reaction of an aryl diazonium salt with potassium iodide is the standard method for the preparation of aryl iodides The diazonium salt is prepared from a primary aro matic amine m the usual way a solution of potassium iodide is then added and the reac tion mixture is brought to room temperature or heated to accelerate the reaction... 

More recently, a study with di- and mono-carbene Pd(II) complexes has demonstrated that the Sonogashira coupling of activated and non-activated aryl iodides can be carried out in an aqueous, aerobic medium and in the absence of amines. These results suggest that the moisture-sensitive copper-acetylide may not be present in this particular transformation, and that a Pd-acetyhde could be formed by deprotonation of the coordinated alkyne instead of transmetallation [130]. 

Xia and co-workers synthesised a number of Pd-NHC complexes (33, 34, 36) for carbonylative Suzuki reactions (Fig. 9.6) [41], Various aryl iodides were carbonylatively coupled (P = 1 atm) with either phenylboronic acid or sodium tetraphenylborate. All the complexes were highly active, but 33 provided the best results with >76% selectivity for ketone in all the reactions. Xia followed this work with the double carbonylation of various aryl iodides with several secondary amines using the catalysts [CuX(Mes)] (37-X) and [Cu(IPr)X] (38-X) (X = I, Br, Cl) (3 MPa, 100°C, 10 h) (Scheme 9.7) [42],... 

Scheme 9.7 General scheme for double carbonylation of aryl iodides with secondary amines...

The original conditions used amines as solvents or cosolvents. Several other bases can replace the amine. Tetrabutylammonium hydroxide or fluoride can be used in THF (see Entry 1 in Scheme 8.11).163 Tetrabutylammonium acetate is also effective with aryl iodides and EWG-substituted aryl bromides (Entry 2).164 Use of alkenyl halides in this reaction has proven to be an effective method for the synthesis of enynes165 (see also Entries 5 and 6 in Scheme 8.11). 

The Alper group [163] reported on a highly efficient double carbohydroamination for the preparation of a-amino carboxylic acid amides 6/1-345, starting from aryl iodides and a primary amine 6/1-344, in usually high yield (Scheme 6/1.88) both, aryl iodides with electron-donating and electron-withdrawing groups can be used. 

With the exception of intramolecular amination reactions, all of the early aryl halide aminations were catalyzed by palladium complexes containing the sterically hindered P(o-tol)3. In papers published back-to-back in 1996, amination chemistry catalyzed by palladium complexes of DPPF and BINAP was reported.36,37 These catalysts allowed for the coupling of aryl bromides and iodides with primary alkyl amines, cyclic secondary amines, and anilines. 

In 1978 and 1980 the coupling of aryl bromides and iodides with both aliphatic and aromatic thiols was first reported in the presence of NaO-t-Bu and Pd(PPh3)4 (Equation (35)).118,119 In contrast to aryl halide aminations and etherifications, the thiation reactions did not require unusual catalysts. Yet, reactions that form aryl alkyl sulfides from alkyl thiols occurred in modest yields in many cases ... 

Recently, Borner and coworkers described an efficient Rh-deguphos catalyst for the reductive amination of a-keto acids with benzyl amine. E.e.-values up to 98% were obtained for the reaction of phenyl pyruvic acid and PhCH2COCOOH (entry 4.9), albeit with often incomplete conversion and low TOFs. Similar results were also obtained for several other a-keto acids, and also with ligands such as norphos and chiraphos. An interesting variant for the preparation of a-amino acid derivatives is the one-pot preparation of aromatic a-(N-cyclohexyla-mino) amides from the corresponding aryl iodide, cyclohexylamine under a H2/ CO atmosphere catalyzed by Pd-duphos or Pd-Trost ligands [50]. Yields and ee-values were in the order of 30-50% and 90 >99%, respectively, and a catalyst loading of around 4% was necessary. 

Amides and carbaminates are a further class of substrates [255, 274-278], Compound 114 shows a substrate with an unprotected hydroxyl group and an aryl iodide [279] (Scheme 1.50), 116 an aryl iodide and the competition of an amide with an amine, yielding a 2.5 1 mixture of amide isomers favoring the (Z)-amide configuration depicted in 117 [280] (Scheme 1.51). 

Another synthetically very promising area deals with the use of allenes in multi-component reactions. For example, the aryl iodide 365 after oxidative addition and cyclization can insert allene (1) to yield the p-allylpalladium(II) species 366. When this is subsequently captured by a secondary amine the functionalized benzo-fused 5-8-membered ring systems 367 are produced in good yield (Scheme 5.54) [157]. 

Ma and Zhao reported a highly regio- and diastereoselective synthetic method for 2-amino-3-alken-l-ols and 4-amino-2-( )-alken-l-ols by the palladium-catalyzed reaction of 2,3-allenols, aryl iodides and amines (Scheme 16.24) [29]. Carbopalladation of PhPdl to the allene probably generates a thermodynamically more stable anti-Jt-allylpalladium species for steric reasons. Regioselectivity of the amine attack depends largely on the stereoelectronic effect on the a-substituents. 

Buchwald has shown that, in combination with palladium(II) acetate or Pd2(dba)3 [tris(dibenzylideneacetone)dipalladium], the Merrifield resin-bound electron-rich dialkylphosphinobiphenyl ligand (45) (Scheme 4.29) forms the active polymer-supported catalysts for amination and Suzuki reactions [121]. Inactivated aryl iodides, bromides, or even chlorides can be employed as substrates in these reactions. The catalyst derived from ligand (45) and a palladium source can be recycled for both amination and Suzuki reactions without addition of palladium. 

A few synthetic applications of palladium catalysis appeared this year. The palladium-catalyzed cyclization of amino allenes 58 occurs with coupling of aryl iodides or vinyl triflates at the 3-position <990L717, 99SL324>. The cyclization can also proceed by the exo-trig pathway, but under suitable reaction conditions the piperidine 59 is prepared selectively. The intramolecular cyclization of amines onto N-allylbenzotriazoles similarly affords piperidines <99JOC6066>. 

The chemo- and regiospecific palladium-catalyzed four-component reaction of aryl iodides followed by incorporation of carbon monoxide, a polymer-supported allene, and a range of secondary cyclic amines has been reported as a short and high-yielding route to complex heterocycles with three points of diversity, such as 7 <2000CC2241>. 

Sonogashira reaction. The first system consisted in the use of the oxime palladacycles 7a-f at elevated temperatures, without the aid of Cul or an amine base, for the coupling of aryl iodides and bromides. They also reported on the use of complex 48b in aqueous media for the coupling of aryl iodides and bromides and terminal acetylenes in excellent yields. ... 

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