Base-assisted intramolecular cycloaddition

In 2005, a base-assisted intramolecular [5+2] cycloaddition of 6-acetoxy-3-pyranones with alkynes was reported by Celanire et al. [72]. As depicted in Scheme 20.30, the treatment of 6-acetoxy-3-pyranones 70a,b with a stoichiometric amount of TEA as a base in refluxing toluene provided the corresponding similar cycloadduct 71a in good yield, since the sUyl derivative 70b underwent conversion to 71a via a desilylation process. The use of acetonitrile instead of... 

Kanematsu and co-workers devised a simple pathway to isobenzofurans and dihydroisobenzofurans starting with substituted furans of type 62. Treatment with strong base results in an alkyne-allene isomerization. Subsequent intramolecular cycloaddition, ring opening (probably oxygen lone-pair assisted), and acidic workup give 63. 

The entropic assistance provided by the intramolecular cycloaddition, the inability of the dienes to tautomerize, and the relative stability of the product (acyl versus alkyl enamine) contribute to the success of this process. A total synthesis of (-)-deoxynupharidine based on the implementation of the in situ generation and subsequent intramolecular Diels-Alder reaction of an A-acyl-l-aza-l,3-butadiene has been detailed [Eq. (13)].32c... 

Another example of a microwave-assisted 1,3-dipolar cycloaddition using azomethine ylides and a dipolarophile was the intramolecular reaction reported for the synthesis of hexahydrochromeno[4,3-fc]pyrroHdine 105 [70]. It was the first example of a solvent-free microwave-assisted intramolecular 1,3-dipolar cycloaddition of azomethine ylides, obtained from aromatic aldehyde 102 and M-substituted glycinate 103 (Scheme 36). The dipole was generated in situ (independently from the presence of a base like TEA) and reacted directly with the dipolarophile present within the same molecule. The intramolecu-... 

Based on the existence of numerous hydroxamate-containing secondary metabolites such as mycelianamide, it can be further proposed that the tryptophyl oxidation proceeds through a hydroxamic acid intermediate (shown in Scheme 10). This functionality, an excellent chelator of (a non-heme) Fe(lll), for instance, could further function to assist the elimination of water to form the imino portion of the azadiene. Since the prolyl methine (pKa>30) must also be removed at the active site of an enzyme, a metal-coordinated amide might also be essential to lower the activation barrier for the deprotonation step. Finally, the intramolecular Diels-Alder cycloaddition might enjoy a catalytic effect of aza-diene-metal coordination. 

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