Oxidative cycloaddition of hydroxamic acids with dienes or guaiacols mediated by iodine(III) reagents

[Bis(trifluoroacetoxy)iodo]benzene (BTI) and (diacetoxyiodo)benzene (DIB) efficiently promote the formation of acylnitroso species from hydroxamic acids in the presence of various dienes to give the corresponding hetero-Diels–Alder (HDA) adducts in moderate to high yields. The present method could be applied to the HDA reactions of acylnitroso species with o-benzoquinones generated by the oxidative dearomatization of guaiacols.


Introduction
The hetero-Diels-Alder (HDA) reaction of N-acylnitroso species with dienes provides the facile and highly stereoselective synthesis of 1,2-oxazines, which have been widely recognized as useful synthons in the synthesis of biologically active natural products [1].Generally, in the presence of dienes, acylnitroso species are in situ generated from hydroxamic acids with oxidants due to their instabilities (Scheme 1, route a).Among the oxidants, tetra-n-alkylammonium periodates are commonly employed for these HDA reactions, however, the removal of the tetra-n-alkylammonium salts, massively gener-ated in these reactions, is often complicated [2][3][4][5].Although the Swern-Moffat oxidation [6], Dess-Martin oxidation [7], and metal-mediated/catalyzed oxidation reactions [8][9][10][11][12] are known as alternative methods [13,14], these methods suffer from a narrow scope and/or low product yields.Furthermore, in the cases where these oxidation methods are inapplicable, a twostep procedure based on the liberation of the acylnitroso species by thermolysis of anthracenyl cycloadducts (route b) is widely used [15,16].Therefore, there is a need to develop novel oxidation methods of hydroxamic acids for HDA reactions.As part of our research on the syntheses of heterocycles by iodine(III)-mediated/catalyzed oxidative cycloaddition reactions [17][18][19], we have found that iodine(III) reagents are effective in the oxidation of N-O bonds of oximes in the cycloaddition reaction of in situ formed nitrile oxides [20,21].Although Adam and Bottke's group have demonstrated that (diacetoxyiodo)benzene (DIB) and iodosylbenzene are applicable to the ene reactions of acylnitroso species derived from hydroxamic acids [22], the iodine(III)-mediated oxidative cycloaddition reaction of hydroxamic acids with dienes is still unknown.Herein, we report the HDA reaction of acylnitroso species generated from hydroxamic acids by [bis(trifluoroacetoxy)iodo]benzene (BTI) or DIB.The present method could be applied to HDA reactions with not only simple dienes but also with masked o-benzoquinones (MOBs) generated by the oxidative dearomatization of guaiacols.
As a further application of the iodine(III)-mediated oxidative cycloaddition reactions, the present method was extended to HDA reactions with masked o-benzoquinones (MOBs) generated by the oxidative dearomatization [26][27][28][29] of guaiacols with methanol (Scheme 2).Liao's and other groups have developed the DA reactions with MOBs as dienes [30][31][32][33], which recently were employed in the HDA reactions of acylnitroso species [34].However, in the HDA reactions with MOBs, the oxidation of the hydroxamic acids to the acylnitroso species requires other oxidants such as tetra-n-alkylammonium periodates.To our delight, the sole use of DIB in a mixed solvent of DCM and methanol gave the endo-cycloadduct 6aa as a single regioisomer in 84% yield starting from hydroxamic acid 1a and guaiacol (5a, Scheme 2).The structure of 6aa was determined by single crystal X-ray analysis [24].It should be mentioned that a slow addition of 1a to the solution of 5a and DIB over a period of 3 h was essential for an effective formation of 6aa.Furthermore, this procedure could be applied successfully to the oxidative cycloaddition reaction of 1a with various guaiacols 5b-g and to the reaction of hydroxamic acids 1b and 1c with 5a.The corresponding products 6ab-6ag, 6ba, and 6ca were obtained with complete regioselectivities in 70-89% yields, albeit low to moderate yields in cases of the bromo-substituted 6ad (53%) and methoxycarbonyl-substituted 6ae (28%).
In most cases of the attempted reactions of 1a with simple dienes or guaiacols, benzoyl anhydride was detected as a byproduct.Since benzoyl anhydride is known to be formed via the dimerization of benzoylnitroso compounds [35], these results suggest that acylnitroso species would be generated from 1a by iodine(III) reagents.Therefore, the high endo selectivities of 1,2-oxadines 3aa-3ca, 3ab, and 6 would depend on the avoidance of electrostatic repulsion between the nitrogen lone pairs of acylnitroso species with π-electrons of the electron-rich dienes in the exo transition states (exo-lone-pair effect) [36].Furthermore, the regioselectivities observed for 3ae, 3be [12,36], and 6 [34] are in consistency with experimental data as well as the results of FMO and DFT calculations.The decline in regioselectivity of 3ce may be due to steric repulsion between the sterically hindered tert-butyloxycarbonyl group in 1c with the 2-methyl substituent of isoprene.

Conclusion
In summary, we demonstrated that BTI and DIB promote the formation of acylnitroso species from hydroxamic acids in the presence of various simple dienes to give the corresponding HDA adducts in moderate to high yields.The present method could be applied to a one-pot reaction involving the generation of MOBs by the dearomatization of guaiacols followed by the HDA reactions of acylnitroso species with MOBs as dienes.
Our findings provide an extended scope of dienes for the HDA reactions and HDA reactions of acylnitroso species with MOBs using single oxidants.

Table 1 :
Screening of I(III) reagents and solvents for HDA reaction of 1a with 2a.
a Isolated yields.b 1.1 equiv.c Yield was determined by 1 H NMR analysis.

Table 2 :
BTI or DIB-mediated oxidative HAD reactions of 1a-c with various dienes.