Ortho alkenylation

Similarly, ketimines (benzylimines of aromatic ketones) undergo the rhodium-catalyzed ortho-alkenylation with alkynes to give or/ o-alkenylated aromatic ketones after hydrolysis.61 This method is applied to an efficient one-pot synthesis of isoquinoline derivatives by using aromatic ketones, benzylamine, and alkynes under Rh catalysis (Equation (55)). 

On the other hand, when this reaction was carried out with 1-chlorovinyl p-tolyl sulfoxide derived from unsymmetrical dialkyl ketone 167 with Af-lithio 1-aminonaphthalene (entries 7 and 8), Z-ortho-alkenylated arylamine Z-171 was obtained as the main product from both vinyl sulfoxides with low stereoselectivity. The stereospecificity and stereoselectivity mentioned above are explained from the high configurational stability of the magnesium carbenoids generated from 1-chlorovinyl p-tolyl sulfoxides derived from a,/ -unsaturated ketones. 

This C-H/olefin coupling can be extended to coupling with acetylenes [6], The reaction of aromatic ketones with internal acetylenes gives the ortho alkenylated product in high yield (Scheme 2), but reaction with terminal acetylenes does not afford the coupling product. With terminal acetylenes, dimerization of acetylenes occurs as a predominant reaction. 

The reaction is often used to effect ring closure.The Friedldnder quinoline synthesis is an example where ortho alkenyl aniline derivatives give the quinoline, 20. The alkene derivative can be prepared in situ from an aldehyde and a suitably functionalized ylid. ... 

During their study on 6-exo-trig radical cyclizations of axially chiral a-halo-ortho-alkenyl anihdes, Curran and coworkers [40] prepared the tricyclic amide 93/94 in moderate yield (49-51%) and excellent chirality transfer (98-99%) via a 6-exo-trig/5-exo-trig sequence (Scheme 5.20). The reaction was proposed to be initiated by an attack at the carbon-bromide bond with BujSnH, providing a-amidyl radical 97 (Scheme 5.21). 

Arynes also undergo transition metal-catalyzed cotrimerization with appropriately functionalized acyclic alkenes. In the presence of a catalytic amount of a palladium-phosphine complex, one molecule of the electrophilic alkenes 231 substituted with either one or two electron-withdrawing groups undergo cotrimerization with two molecules of aryne to form a mixture of dihydrophenanthrene 232 and ortho-alkenyl biaryls 233 (Scheme 12.64) [127]. 

Oxidative alkenylation directed by an amide group has also been developed [15]. de Vries, van Leeuwen, and coworkers [15a] reported the Pd-catalyzed ortho alkenylation of anilides (Scheme 18.15). The reaction can be conducted even at room temperature in the presence of benzoquinone and p-toluenesulfonic acid (TsOH) as oxidant and additive, respectively, in AcOH/toluene. 

It was reported that not only amides but also N-arylureas undergo the ortho alkenylation in the presence of the Pd(OAc)2/benzoquinone/TsOH system (16). Using this system, the ureas also couple with dienes followed by nucleophilic cyclization to produce N-carbamoyl-2-alkenylindoUne derivatives (Scheme 18.16) [16a). 

N-Tosylbenzamide undergoes ortho alkenylation/annulation in a similar manner to those of benzoic acids (Scheme 18.11) to produce the corresponding isoindolinone (Scheme 18.17) [17]. 

Yu and coworkers [20] reported that the ortho alkenylation of phenylacetic acids proceeds efHciently in the presence of a Pd(OAc)2/benzoquinone catalyst system under basic conditions with KHCO3 in tert-amyl alcohol under Oj atmosphere to afford (2-alkenylphenyl)acetic acids (Scheme 18.20). In contrast to the reaction of benzoic adds (Scheme 18.11), the nudeophilic cychzation of... 

Rh-catalyzed ortho alkenylation reactions have been develop>ed remarkably [10a]. In all cases, [Cp RhCl2]2 is employed as a catalyst precursor, as in the early example with benzoic acids as the substrates (Scheme 18.11) [12]. Glorius [28] and Li s groups [29] reported the amide-directed alkenylation of acetanilides and benzanilides, respectively (Scheme 18.28 and Scheme 18.29). 

The Ir-catalyzed version via path A was disclosed by the authors group. In the reaction of 1-naphthols, an [IrCl(cod)]2/PtBu3 catalyst system is effective for the C-H bond alkenylation at the peri position (Scheme 18.86) [85]. Recently, Shibata and coworkers [86] reported that aromatic ketones undergo ortho alkenylation in the presence of a cationic Ir catalyst. 

Kuninobu, Takai, and coworkers [90] demonstrated that aromatic imines undergo ortho alkenylation under Re catalysis (Scheme 18.88). This reaction was proposed to proceed via C-H bond activation at the ortho position of imines, alkyne insertion into not Re-H but Re-C bond, intramolecular nucleophihc attack of the formed Re-C(sp ) bond on an imino carbon, and final reductive eUmination. 

Aryl phosphine oxides have been employed as substrates for ortho-alkenylation via aHqme insertion in the presence of a ruthenium catalyst... 

Figure 4.33 A cross-section of results for the Ru-catalyzed ortho-alkenylation/cyclization to form chiral phthalides as described by Ackermann and Pospech [67].

The decarboxylative coupling of benzoic acids with internal alkynes in a 1 2 manner was achieved under iridium catalysis to produce the corresponding benzannu-lated products (Scheme 4.31) [36]. The carboxylic group acts as a directing group, as in the rhodium-catalyzed ortho-alkenylation described above (Schemes 4.28 and 4.29). Thus, carboxylic group directed metalation at the ortho C-H bond and subsequent alkyne insertion may take place to form a seven-membered iridacycle intermediate. Then, decarboxylation, the second alkyne insertion, and... 

Lim S-G, Lee JH, Moon CW, Hong J-B, Jun C-H (2003) Rh(I)-catalyzed direct ortho-alkenylation of aromatic ketimines with alkynes and its application to the synthesis of isoquinoline dtnivatives. Org Lett 5(15) 2759-2761... 

Jun et al. demonstrated a Rh(I)-catalyzed cyclization of an N-benzyl aromatic ketimine with diphenylacetylene to provide isoquinoline 44 [27]. The chelation-assisted C-H activation strategy was employed for the first time for isoquinoline synthesis. However, the reaction required a high temperature (150 C) and led to two different isoquinoline derivatives 44 and 44. Based on the experimental results, the authors proposed a plausible reaction mechanism that involved ortho-alkenylation, 6. r-electrocyclization, intermolecular nucleophilic substitution, and dehydrogenative aromatization (Eq. (5.43)). 

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