Aldehydes reactions with arynes

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). 

Yoshida et al. have shown the potential of CO as a Cj source in aryne MCR developing a straightforward access to benzoxazinones 73 nsing imines as the nncleophUic component (Scheme 12.38) [63]. The same authors have used aminosilanes for the three-component coupling with arynes and aldehydes, including sulfonylimines, to provide 2-aminobenzhydrols and 2-aminobenzhydryl amines 74. Benzoic acid plays a vital role in the reaction, probably favoring the formation of an amine from the aminosilane (Scheme 12.38) [64]. 

The 1 -dipolar cydoaddition reaction of stable azomethine imines 34 with arynes leading to the formation of l,2-dihydropyrazolo[l,2-fl]indazol-3(9fi)-ones 35 was demonstrated by Larock and coworkers (Scheme 18) [43]. The stable azomethine imines were easily prepared by the condensation of 3-pyrazolidinones with different aldehydes, and are isol-able and stable compounds. In this reaction, the aryne was generated in situ from 1 using tetrabutylammonium difluo-rotriphenylsilicate (TBAT) as the fluoride source. The reaction worked well with a variety of stable azomethine imines. 

H. Yoshida, M. Watanabe, H. Fukushima, J. Ohshita, A. Kunai, A 2 1 coupling reaction of arynes with aldehydes via o-quinone methides straightforward synthesis of 9-arylxanthenes, Org. Lett. 6 (2004) 4049- 4051. 

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. 

The first clue to the existence of the SrnI mechanism came from product studies both in aliphatic and aromatic cases. It was noticed that in the reaction of benzyl and substituted benzyl chlorides with the 2-nitropropane anion, oxygen alkylation, yielding the oxime and then the aldehyde, occurs exclusively in the case of benzyl chloride and 3-nitrobenzyl chloride, whereas, with 4-nitrobenzyl chloride, the yield of aldehyde is only 6% and the carbon-alkylated (104) product is obtained in 92% yield (Kornblum, 1975). This was interpreted as the result of a competition between 8, 2 (O-alkylation) and S l (C-alkylation) reactions. In the aromatic case, it was observed that the reaction of 5- and 6-halopseudocumenes with KNHj in liquid ammonia (Kim and Bunnett, 1970) forms the 5- and 6-pseudocumi-dines in a ratio which is the same whether the starting compound is the 5- or 6-isomer in the case of the chloro- and bromo-derivatives, as expected from an aryne mechanism (Scheme 9), whereas much more non-rearranged... 

An aryne multicomponent reaction involving isoquinoline and 5-bromo-1-methylisatin resulted in spirooxazino isoquinolines (Scheme 66).The reaction occurs with a number of iV-substituted isatins. Quinoline can replace the isoquinoline as well. Carbonyls other than the isatins can trap the anion as well. A variety of aromatic, aliphatic, and heteroaromatic aldehydes can function as the electrophile. When pyridine replaces isoquinoUne as the nucleophilic trap, the reaction forms an oxindole but not an oxazino pyridine derivative (14SL608). 

Yoshida et al. have reported the coupling of an aromatic aldehyde and 2equiv. ofaryne, affording 9-arylxanthenes (Scheme 12.53) [101]. The reaction presumably starts with a nucleophilic attack of the carbonyl oxygen of 188 on the aryne, leading to zwitterion 189, which subsequently undergoes cyclizahon to afford benzoxete 190. Subsequent isomerization of 190 leads to o-quinone methide 191 which then undergoes [4+2] cycloaddition with a second molecule of aryne to afford the xanthene 192. 

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