Arynic condensation

The reaction mechanism is believed to involve a domino hydroamination-in-tramolecular arynic condensation. Indeed, the same results are obtained from either 2- and 3-chlorostyrenes [159]. 

The arynic condensation, yields of ring enlargement products IY/113. For additional informations see ref. [61] [62]. 

The arynic condensation of 1,2-diketone monoacetal enolates with aryne (from bromobenzene and sodium amide) lead to IV/114. Depending on the reaction conditions, compound IY/1I4 can be transformed to two different enlargement products, IV/115 and IV/117. The mechanisms involved in these transformations are obvious [63] [64], Scheme IV/18. 

An enlargement reaction somehow related to the arynic condensation mentioned above is the transformation shown in Scheme IV/19 [65]. 

IV.2.1. Aromatic Elimination-Addition Reactions (Arynic Condensations). . 65... 

Several reviews have been written on arynic condensations (see for example7,8 36 ) and we shall recall only briefly the basic principle of these reactions (Scheme 20). 

IV.2.1.2.1. Monohabgenobenzenes. From the literature7 it appears that arynic condensations of thiolates in the presence of NaNH2 or KNH2 in liquid ammonia give poor to fair yields in desired products. On the other hand, amines generally do not condense in liquid ammonia. They nearly always need the use of the corresponding lithium amide and/or they constitute the solvent. 

As for the other reactions described above, complex base gives more satisfactory results (better yields and shorter reaction times). However, the most important result is that NaNH2 in HMPA—THF leads to direct substitutions when NaNH2 -f-AmONa in THF leads to arynic condensations. 

Taking into account the chlorine mete-directing effect in arynic condensations7, so we can see that 75 and 77 should be the main products formed by arynic condensation on 69. On the other hand 70 must essentially lead to 75. 

EA (Elimination Addition) = Arynic Condensation. Very low part in the reaction, if happens. 

In conclusion, this study gives some new light on nucleophilic substitutions of polyhalogenobenzenes and shows that complex bases are particularly useful when arynic condensations are wanted. Moreover, the described methods are of general interest in the synthesis of a lot of aminobenzenes and nitrogen heterocycles from several commercially cheap starting materials. 

From the literature7,8> 41> 55> s6> appears that ketones were phenylated in liquid NH3 in the presence of NaNH2 by means of arynic condensations. Note that it has been shown for a few years that it is possible to synthesize phenyl ketones starting from halogenobenzenes and ketone enolates by means of SRn, reactions57. ... 

In both cases, arynic condensations were performed in the same conditions. In the second reaction, hydrolysis was precedented by methyl iodide addition. As a consequence it was not possible to isolate 105 (n = 7) and ketonic compounds only were formed. 

Thus from these experiments it must be concluded that if alcohols 105 are isolated after an arynic condensation, this means that during all the reaction, Na+ remains near the oxygen of the starting enolate and that of course, all other things being the same, the alcoholate is stable in the reaction conditions. This hypothesis is confirmed by reaction pictured in Scheme 3768. ... 

Alcohols 105 are directly obtained from arynic condensations only when n = 5, 6, 7. We shall see briefly later that we have now another way to obtain several of them. 

Interesting synthetic applications of arynic condensations of ketone enolates were also obtained in the synthesis of benzocyclenones. We shall comment them a bit. 

Benzocyclenones may be often obtained directly after arynic condensations. However, as we saw before, benzocyclobutenols 105 are also obtained in several reactions. In those cases, 105 may be opened by reaction with a base in aprotic solvent to give the benzocyclenone 106 with very good yields64). 

On the other hand, arynic reactions are also of interest in the synthesis of benzocyclenones substituted on the aromatic ring by an alkyl group in the ortho position of the carbonyl group. In these syntheses, ortho alkyl bromobenzenes must be used and arynic condensation intermediaries are of the 108 type ... 

Closing this section we have to point out that arynic condensations of ketone enolates may incidentally take a curious way78. Thus NaNH2-norcamphor lithium enolate condenses on bromobenzene to give directly the polycyclic alcohol 110 (Scheme 43). 

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. 

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