Hydroarylation norbornene

Scheme 6.15 Pd-catalysed hydroarylation or norbornene using chelating NHC/P-Ugands...

An Ir(l)-catalyzed asymmetric intermolecular hydroarylation of norbornene with benzamide was reported in good to excellent enantiomeric excess, albeit in low yields, via the aryl C—H activation (Scheme 5.14). In some cases, the hydroami-nation products of norbornene were also formed in high enantioselectivities. 

However, the chemical shift for a o-bound M-aryl bond appears at high frequency, often between 130 and 180 ppm. Both the cydometallated nitroso-amine compound 65 [63-65] and the Pd(ii)(Duphos) complex 66 (an intermediate in the enantioselective hydroarylation of norbornene) [66] represent typical examples. 

The Heck reaction yields the final product through a p-hydride elimination whereas hydroarylation or hydrovinylation generates the final product via a reductive elimination. Nonetheless, both reactions share a common first step, that is, addition of an aryl or a vinyl palladium species to an alkene, and thus are briefly discussed here. Norbornene 595 is the most studied alkene to evaluate an the... 

Intermolecular hydroamination or hydroarylation reactions of norbornene and cyclo-hexadiene carried out with catalytic amounts of Brpnsted or Lewis acid in ionic liquids have been found to provide higher selectivity and yields than those performed in classical organic solvents. This effect was attributed to the increases of the acidity of the medium and stabilization of ionic intermediates through the formation of supramolec-ular aggregates with the ionic liquid.38... 

The tungsten(II) carbonyl complex (CO)4W(/u.-Cl)3W(SnCl3)(CO)3 has been identified as a very effective catalyst for the hydroarylation of norbornene conducted in arene solution at room temperature. Norbornene adducts with benzene, toluene, p-xylene, and mesitylene have been isolated. On the basis of XH NMR monitoring of several catalytic reactions, a possible mechanism, involving coordination of norbornene to the W(II) atom and its activation, has been proposed.123... 

The diastereoselective addition of aniline to norbornene was accomplished using a catalytic amount of iridium(I). As the intermediate azametallacyclobutane 2 could be isolated its stereochemistry was determined by X-ray analysis both iridium and nitrogen occupy the exo position41. However, the scope of the amination method, with respect to the nature of the amine and the structure of the alkene, was not determined. Conversely, the analogous rhodium(I)-cat-alyzed reactions of norbornene and aromatic amines gave mixtures of hydroamination and hydroarylation products106. 

Asymmetric hydroarylation/hydrovinylation, although not strictly a Heck reaction as the P-hydride ehmination step is replaced by reductive ehmination, nevertheless shares a common mechanistic pathway with regard to the enantiose-lective step and so will be discussed briefly. In 1991 Brunner et al. first reported hydrophenylations of norbornene and norbornadiene using aryl iodides, al-... 

Using this method diastereoselective exo hydrovinylation and hydroarylation of norbornene, norbornadiene and similar bicycles is achieved in good yields with vinyl and arylhalogen compounds in the presence of Pd(OAc)2(PPh3)2 as catalyst and formic acid as reducing agent4 6-70. 

If palladium(II) acetate is modified with various chiral ligands (Diop, BPPM, Norphos, etc.), this leads to enantioselective hydroarylation of norbornene and norbornadiene with up to 41 % ee7. Besides phenyl iodide, other aryl iodides with methoxy substituents in the 2-, 3-, or 4-position and 4-(iV-trifluoraacctyl)aminophenyl iodide are used, giving similar results. 

Togni and co-workers firstly reported the Ir-catalyzed asymmetric inter-molecular hydroarylation of norbornene with benzamide (Scheme 5.59). The ortho C—H bond arylation product 174, clearly indicating that the amide group must interact with Ir center probably via the oxygen atom, was obtained... 

In light of the initial contribution by Chiusoli et al., it is somewhat surprising that efficient procedures for the palladium-catalyzed hydroarylation of norbornene (144) were reported almost a decade later by Cacchi et al. [3] and, shortly after, by Larock et al. (4) (144 155 Scheme 7.36). These protocols resemble that of Chiusoli et al. (86), as well as those for the conjugate hydroarylation of a, 3-unsaturated carbonyl compounds (see Chapter 8) [88]. In recent years, catalysts such as pal-ladacycles [89-91] and palladium-carbene complexes [92] were also shown to catalyze the hydroarylation of 144. 

Extension of the asymmetric hydroarylation to oxanorbornenes, as well as aza-norbornenes, was the obvious step forward. Fiaud et al. made several remarkable observations while examining the reductive Mizoroki-Heck-type arylation of the annulated 7-oxanorbornene 160 (Scheme 7.37) [100]. First, intermediate o-aUcyl... 

Figure 7.3 Chiral ligands tested in the asymmetric hydroarylation of norbornene.

In fact, intermolecular hydroarylation of alkenes other than norbornenes was also realized, with Kulagowski et al. exploiting the diastereospecificity of both aUcene insertion and 3-hydride elimination in the sterically driven regioselec-tive coupUng of 170 and 171 (170 172 Scheme 7.41) [110]. However, it was emphasized that an excess of chloride anions was required to prevent dehalogenation [95]. 

The carbopalladation of a double bond in a Cj-bridge of a bicyclic alkene leads to an intermediate, which does not contain a syn-oriented P-hydrogen and thus cannot undergo a syn-P-hydride eHmination to recreate a double bond. Such carbopalladation intermediates of, for example, norbornene with arylpalladium hahdes therefore find other modes of reaction (Section 8.3.7). In the presence of formic acid or potassium formate as a hydride source, norbornene (65), norbornene derivatives, and heteroanalogs such as 247 and 248, as well as bicyclooctene[2.2.2]octene (251), under typical Heck conditions undergo hydroarylation and hydroalkenyla-tion reactions (Scheme 8.52) [374]. A number of hydroarylation products of type... 

Compared to the hydroamination of alkynes, the protocols for more readily available olefins were rather limited. Ackermann presented a TiCU-catalyzed hydroamination reaction of norbornene using a variety of functionalized amines. Regioselective hydroarylation occurs as a competing reaction and the chemose-lectivity for hydroamination products ranges from poor to excellent [312]. This protocol can also be utilized in the hydroamination of vinylarenes with some electron-deficient amines [313] and the hydroamination of enyne compound. In the latter reaction, a subsequent rearrangement gives rise to a tetrahydroisoquinoline derivative (Scheme 14.134). 

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