Isoquinolones, annulation, with alkynes

The ruthenium(ll) catalytic annulations of benzamides with alkynes leading to isoquinolones were performed under much milder conditions by the introduction of... 

A detailed study of the mechanism of the Ru(II) catalysed annulation of isoquinolone with alkynes was proposed. Noteworthy, all of the key intermediates... 

The reaction was further extended to the annulation of Af-pivaloxybenzamide with terminal alkynes to give 3-substituted isoquinolones 61 with good regioselectivity under mild conditions (Eq. (5.59)) [34]. If alkenes were used, the reaction gave 3,4-dihydroisoquinolones 62 in good yields (Eq. (5.60)) however, both diaryl- and dialkyl-substituted alkenes failed to react under the same reaction conditions. 

An interesting Rh(III)-catalyzed intramolecular annulation of alkyne-tethered benzamides to give isoquinolones was recently developed by Park and coworkers [36a]. The reaction might involve intramolecular insertion of the alkyne moiety with rhodacycle II, which leads to intermediate 12 or 12. Then, reductive elimination, followed by oxidative addition of the N-O bond, gives intermediate... 

Then until 2011, the Ackermann group reported a ruthenium(II)-catalyzed oxidative annulations of alkynes with benzamides (Eq. (7.22)) [29]. In this method, Cu(OAc)2 H2O was used as the terminal oxidant to regenerate the ruthenium(II) catalyst in the catalytic cycle. This cyclization reaction proceeded via cleavage of both ortho-C H and amide N-H bonds of benzamides to form isoquinolones in high chemo- and regioselectivity. The insertion of unsymmetrical alkylarylalkynes occurred with a connection of the electron-deficient alkyne carbon with nitrogen atom selectively. Moreover, electron-deficient alkynes exhibited higher reactivity in this transformation. 

Scheme 7.9 Proposed mechanism for ruthenium-catalyzed oxidative annulations of isoquinolones with alkynes.

Ackermann s group reported the oxidative aimulations of alkynes with benzamides with a rutheniuni(II) catalyst in 2011 with the use of an oxidant Cu (0Ac)2.H20, under conditions of C-H bond activation. This dehydrogenative annulation of benzamides via transformation of both ortho C-H and amide N-H bonds selectively produced isoquinolones [(Eq. 87)] [176]. Diphenylacetylene is shown to be much more reactive than diethylacetylene, and electron-deficient alkynes preferentially react with benzamides to give isoquinolones. 

Annulation reactions between unactivated alkynes and a range of heteroatom-containing substrates have facilitated the preparation of a host of heterocycles. For example, the preparation of isoquinolones was achieved through a rhodium-catalyzed annulation of internal acetylenes with 0-methyl hydroxamates (Scheme 3.78 and Example 3.12) [81]. The reaction conditions were quite mild, and most reactions were complete within 16 h. The overall process was redox neutral and used a catalytic amount of cesium acetate to promote the reaction. Additionally, the process was not appreciably sensitive to the electronic composition of the 0-methyl hydroxamates. One of the more attractive aspects of this chemistry was the observation that the rhodium-catalyzed reaction... 

In 2010, Fagnou and coworkers reported a cascade method for the synthesis of isoquinolones 58 by Rh-catalyzed annulation of Af-methoxybenzamides with internal alkynes [32]. Both symmetrical and unsymmetrical alkynes were examined as the coupling partners (Eq. (5.56)). This external oxidant-free process used a N-O bond to unlock the C-N bond formation and catalyst release. 

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