Stereoselective Oxidative Cyclization of N-Allyl Benzamides to Oxaz(ol)ines

Abstract

This study presents an enantioselective oxidative cyclization of N-allyl carboxamides via a chiral triazole-substituted iodoarene catalyst. The method allows the synthesis of highly enantioenriched oxazolines and oxazines, with yields of up to 94% and enantioselectivities of up to 98% ee. Quaternary stereo centers can be constructed and, besides N-allyl amides, the corresponding thioamides and imideamides are well tolerated as substrates, giving rise to a plethora of chiral 5-membered N-heterocycles. By applying a multitude of further functionalizations, we finally demonstrate the high value of the observed chiral heterocycles as strategic intermediates for the synthesis of other enantioenriched target structures.sustaining the stereochemistry (92% ee). 71 Lastly, we prepared 3-aminopropane-1,2-diol by a reduction of 3a followed by acid-mediated ring-opening to give the amino diol 4g. Since this compound could not be analyzed by HPLC, it was directly transformed into the N-tosylated derivative 4h. 4h was isolated in 42% yield but with a diminished selectivity of 78% ee .In summary, we have established a practical method for the enantioselective oxidative cyclization of N-allyl amides by using an improved triazole-substituted iodoarene catalyst. This method is characterized by a broad substrate scope which allows the construction of highly enantioenriched 5-oxazolines, thiazolines, and imidazolines. Quaternary stereocenters can be constructed with high efficiency as well and the method was further extended to oxazines. Many of the constructed compounds can serve as chiral building blocks for the synthesis of interesting chiral target structures. This was demonstrated in a variety of further functionalizations, in particular of the terminal OH group.In further investigations, we aim to apply C1-symmetric triazole-based iodoarenes in similar oxidative cyclizations to generate other useful 5-and 6-membered heterocycles. Additionally, cascade reactions in which the reactive hypervalent iodine intermediate is trapped directly by nucleophiles other than OH will also be part of future investigations. ASSOCIATED CONTENTSupporting Information. All supporting information is available free of charge on the ACS Publications website at DOI: XXX. This includes all experimental procedures and characterization data.

Toward a General Protocol for Catalytic Oxidative Transformations Using Electrochemically Generated Hypervalent Iodine Species

“…Ions were generated by electrospray ionization (ESI), and only the mass ions are reported. Spectral data for previously reported compounds are in good agreement with literature: 1a , 56 1b , 50 1c , 56 1d , 56 1e , 56 1f , 57 1i , 58 1j , 59 1k , 60 1l , 60 1m , 60 1n , 61 1o , 58 1p , 58 1s , 62 1u , 58 1v , 63 1w , 51 1x , 51 1z , 50 4a , 22 4b , 22 4c , 64 4d , 65 4e , 64 4g . 22 Ketones 3a–g were all purchased from Fluorochem and were used as received.…”

Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles

“…The method allows the synthesis of oxazolines and oxazines with excellent yield and enantioselectivity (Scheme 56). 113…”

“…The method allows the synthesis of oxazolines and oxazines with excellent yield and enantioselectivity (Scheme 56). 113 Owing to their importance, the synthesis of isoxazolines and isoxazoles has become an interesting area of research. [114][115][116] In this regard, a one-pot, regioselective 1,3dipolar cycloaddition of in situ generated (diethoxyphosphoryl) difluoromethyl nitrile oxide (91) with alkenes and alkynes has been reported by the Pajkert group.…”

Nitrogen Functionalization with <i>N</i>-(Fluorosulfonyl)carbamates

“…In addition to carboxylic acids, amides could also be used as the intramolecular oxygen source to give enantioenriched oxazolines with moderate enantioselectivities (Figure 14). 24…”