Amines, arylation with alkenes

Doyle et al. (1977 c) and Oae et al. (1980) reported modified Meerwein arylations with significant improvements in the yield by the use of aryl amines and alkyl nitrites in place of arenediazonium salts. However, good yields are only achieved if alkenes activated by electron-withdrawing groups are present. 

S-Protonated Aryliminium Salts Hesse has made a much more extensive study of the reaction of aryl primary amines (58) with higher aldehydes (see 59) and a suitable alkene, usually styrene or a-methylstyrene, and found that high yields of tetra-hydroisoquinoline (60) could be obtained even when an electron-withdrawing group was present in the aryl ring. Carbonium ion (61) appeared likely as an intermediate. 

Vinyl substitution occurs with conjugated dienes as well as with alkenes, employing aryl-, vinyl-, methyl-, alkoxycarbonyl- or benzyl-mercury reagents and lithium tetrachloropalladate(II), but the products are usually rr-allylpalladium complexes if the reactions are carried out under mild conditions (equation 8).24,25 The ir-allylic complexes may be decomposed thermally to substituted dienes26 or reacted with nucleophiles to form allylic derivatives of the nucleophile. Secondary amines, for example, react to give tertiary allylic amines in modest yields, along with dienes and reduced dienes (equation 9).25... 

Furthermore, Pd-catalyzed aminations can be sequentially coupled with alkene insertion and amination. Wolfe and Lira [102] have established a transformation involving two different sequential metal-catalyzed reactions that lead to AT-aryl-2-benzylindolines 125 in moderate to excellent yields upon formation of two C - N bonds and one C - C bond in a one-pot process (Scheme 45). Interestingly, the selective installation of two different aryl groups in this sequence can be accomplished by in situ modification of the Pd catalyst system Pd-126 upon addition of the chelating ligand dpephos prior to addition of the second aryl bromide (Scheme 46). The selectively substituted indoline derivatives 127 were isolated in good to excellent yields. 

The reaction of aryl azides with alkenes in the presence of aluminum trichloride gave different products depending on the structure and the geometry of the alkene, the reaction proceeds via the intermediacy of an aziridine 8 complexed with the Lewis acid. Thus aziridines 9 were cleanly obtained from cycloheptene and (Z)-cyclooctene, however, from cyclopentene and cyclohexene a mixture of allylic amines 10 and /5-chloro amines 11 was produced86- 87. The use of 4-chlorophenyl azide in the reaction with cyclohexene gave only a tar. 

The reaction of aryl azides with excess alkenes in the presence of trifluoroacetic acid proceeds by an analogous mechanism and afforded, after basic hydrolysis, /5-hydroxy amines together with byproducts. A diastereoselective reaction was observed only with cyclic and acyclic (Z/-alkenes, e.g., 12 and 1388. From methyl ( )-2-butenoate, A-phenylthreonine methyl ester was similarly prepared in 30% yield88. 

There is direct evidence, from ir and nmr spectra, that the fert-butyl cation is quantitatively formed when ferf-butyl chloride reacts with AICI3 in anhydrous liquid HCl. In the case of alkenes, Markovnikov s rule (p. 1019) is followed. Carbocation formation is particularly easy from some reagents, because of the stability of the cations. Triphenylmethyl chloride and 1-chloroadamantane alkylate activated aromatic rings (e.g., phenols, amines) with no catalyst or solvent. Ions as stable as this are less reactive than other carbocations and often attack only active substrates. The tropylium ion, for example, alkylates anisole, but not benzene. It was noted on p. 476 that relatively stable vinylic cations can be generated from certain vinylic compounds. These have been used to introduce vinylic groups into aryl substrates. Lewis acids, such as BF3 or AIEta, can also be used to alkylation of aromatic rings with alkene units. 

The photoreactions of the pyrimidinethiones (235) with alkenes has been studied. Arylation of the iodouridine (236a) affording (236b) can be brought about by irradiation in the presence of the appropriate aromatic compound and triethyl amine. 

Topics reviewed during the year include the photochemistry of indoles, sulfoxides, pyrazoles and isothiazoles, (S-hetero)cyclic unsaturated carbonyl compounds, photoinduced single electron transfer (SET) reactions of amines and of azo compounds, SET reactions of organosilanes and organostannanes with Qo and ketones, photochromic polypeptides and di(hetero)arylethenes, processes in chromophore sequences on a-helical polypeptides,aryl-aryl coupling in furans, thiophenes and pyrroles," [3+2]cycloaddition of aromatic nitriles (and esters) with alkenes, and reactions of benzylsilane derivatives. ... 

Heck couplings of aryl halides with alkenes in room temperature ionic liquids have been reported [44]. Dialkylimidazolium and n-hexylpyridinium hexafluoro-phosphate and tetrafluoroborate ionic liquids were used as solvents, Pd(OAc)2 and PdCl2 as catalysts, and an amine as base. Addition of ligands such as triphe-nylphosphine, tri-o-tolylphosphine, and triphenylarsine usually had a negative affect on product yield. Addition of cosolvents such as DMF was not necessary. Palladium-catalyzed Heck reactions involving aryl bromides have been performed... 

In most of the palladium-catalysed domino processes known so far, the Mizoroki-Heck reaction - the palladium(0)-catalysed reaction of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - has been apphed as the starting transformation accordingly to our classification (Table 8.1). It has been combined with another Mizoroki-Heck reaction [6] or a cross-coupling reaction [7], such as Suzuki, Stille or Sonogashira reactions. In other examples, a Tsuji-Trost reaction [8], a carbonylation, a pericyclic or an aldol reaction has been employed as the second step. On the other hand, cross-couphng reactions have also been used as the first step followed by, for example, a Mizoroki-Heck reaction or Tsuji-Trost reactions, palladation of alkynes or allenes [9], carbonylations [10], aminations [11] or palladium(II)-catalysedWacker-type reactions [12] were employed as the first step. A novel illustrative example of the latter procedure is the efficient enantioselective synthesis of vitamin E [13]. 

In 1972, Heck showed, independently, that aryl, benzyl and styryl halides would react with alkenes in the presence of a hindered amine as organic base at a lower reachon temperature of 100 °C (Scheme 1.16) [51, 66]. A detailed overview on the modem aspects of Mizoroki-Heck reactions, as well as their oxidative variants (Fujiwara reactions), is provided by Martin Oestreich and Verena Trepohl in Chapter 7. 

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