Ketones reactions with arynes

P-Enamino esters and ketones react with arynes in an interesting manner. Aryla-tion occurs at the a-carbon to form the C-arylation product, instead of the expected N-arylation product (Equation 12.13) [15]. In addition, a variety of functional groups that are known to react with arynes, such as amino and hydroxyl groups, as well as alkenes and furans, are all well tolerated in this reaction. 

Type A of ring closure to acridines is represented by reactions of arynes with suitable partners. Recendy, 2-aminoaryl ketones 90 with arynes generated from 91 to give acridines 92 have been developed and optimized (Scheme 32). The major by-products are the corresponding (2-(phenylamino)phenyl) ketones and result by protonation after attack of the amino group on the... 

Zirconium-benzyne complexes have been used rather extensively in organic synthesis.8 45 For this purpose, one particularly important characteristic of zirconium-aryne complexes is that olefin insertion into the Zr—C bond occurs stereospecifically. Thus, when generated in situ, the zirconium-benzyne complex (45) reacts with cyclic alkenes to give exclusively the cis-zirconaindanes (46), which upon treatment with electrophiles provide access to a variety of m-difunctionalized cycloalkanes (47-49) (Scheme 5).46 For example, carbonylation of intermediate 46 affords tricyclic ketone 49, reaction with sulfur dichloride gives thiophene 48, and reaction of 46 with tert-butylisocyanide followed by I2 gives 47 via 50 and, presumably, intermediate 51 [Eq. (12)]. 

Observation of Scheme 54 shows a close analogy between these results and the ones obtained in arynic condensations. Thus we observe the formation of normal ketones 138, transposed ketones 139 or 140, and methylene cyclobutanols 141. However, we met large difficulties with the mechanism. Indeed, starting from the hypothesis of cyclohexyne being the intermediary (what is consistent with our works on amine condensations) and by analogy with arynic condensations, the reaction should be written as in Scheme 55. 

Various anions (ketones enolates for example) are able to react with arynes (Fig. 13) leading to the phenylated compound (refs. 80, 81). When the anion is generated from the starting material, the reaction leads to a cyclisation product (refs. 82-84). These reactions are also possible with other aromatic compounds (ref. 85). 

Quinolines react with arynes and aldehydes in a diastereoselective manner to form benzoxazino quinolines in good yields (Scheme 71) (13OL4620). Halides and alkoxy groups were tolerated on the aromatic aldehydes. Heteroaromatic aldehydes also reacted smoothly (2 examples, 57—69%). The aldehydes can be replaced with ketones without a loss in yield. Various functional groups are also tolerated on the quinoline or aryne. Finally, the reaction proceeds in an analogous fashion with isoquinolines but with less diastereoselectivity (8 examples, 62-92%, 3 1). 

M. Jeganmohan, S. Bhuvaneswari, C.-H. Cheng, Synthesis of N-arylated 1,2-dihydroheteroaromatics through the three-component reaction of arynes with N-heteroaromatics and terminal alkynes or ketones, Chem. Asian J. 5 (2010) 153-159. 

P. Liu, M. Lei, L. Hu, Synthesis of benzo-annulated 1,3-oxazine derivatives through the multi-component reaction of arynes with N-heteroaromatics and aldehydes or ketones. Tetrahedron 69 (2013) 10405-10413. 

It is noteworthy that at the difference of what we met for arynic reactions, alcohols with a strained ring are isolated with cyclooctanone and with aliphatic ketones. Since the obtaining of these alcohols by us for the first time, a synthesis by photolysis of cyclenones has been published102. However, this last method seems, for the present time, much less general and above all much less stereoselective. 

In the inaugural generation and Diels-Alder cycloaddition reactions of 4,5-, 5,6-, and 6,7-indole arynes, Buszek and colleagues used Fischer indolization to prepare the prerequisite indoles 199 and 200 (Scheme 54, equations 1 and 2) [382,383]. A series of 2-trifluoromethyUndoles 201 was prepared starting with the appropriate trifluoromethyl-ketones (equation 3) [384]. 

Upon treatment with i-PrMgCl, arynes are readily generated from 2-iodoaryl sulfonates 100 by the corresponding 2-magnesiated aryl sulfonates 101. These arynes have been allowed to react with furan in situ to afford the Diels-Alder products 102 (Scheme 12.30) [59]. Functional groups, such as an ester, cyano, nitro or ketone group, are all well tolerated under the reaction conditions. 

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