A Stereoselective Route to Aza‐C‐aryl Glycosides from Arynes and Chiral Nitrones

Abstract

Arynes are regarded as potential and versatile intermediates in organic synthesis. These highly‐reactive, strained and kinetically unstable species have numerous applications in synthetic chemistry. In this article, a highly‐diasteroselective and efficient 1,3‐dipolar cycloaddition reaction between a range of arynes and sugar‐derived cyclic nitrones leading to an interesting class of sugar‐based benzo[d]isoxazolines is described. These benzo[d]isoxazolines upon selective N–O bond cleavage provide various substituted aza‐C‐aryl glycosides in good yield. These substituted pyrrolidine derivatives are chiral aminophenols and could be potential chiral ligands and organocatalysts in asymmetric synthesis.

Cycloaddition of Benzyne with Alkoxy-Substituted Pyrroline-N-oxides­: Unexpected Rearrangement to an N-Phenylpyrrole

“…7,8 Following the seminal work of Kaliappan's goup, 4 we studied the cycloaddition of dialkoxypyrroline N-oxides with benzyne as another entry to radicamine or codonopsinine analogues. In particular, the lack of substitution on C-5 of the nitrone could allow the introduction of various substituents by following the well-known alkylation of the nitrone following the oxidative opening of the hexahydropyrrolo[1,2-b]isoxazolidine ring.…”

“…In Kaliappan's work 4 there is no mention of such a rearrangement product. However, the absence of the side product in those reactions can be explained by the lower nucleophilicity of the isoxazolidine nitrogen in B (R′ = Bn; R = CH 2 OBn, Scheme 1), which is shielded by a bulky adjacent benzyloxymethylene group.…”

“…Among these processes, 1,3-dipolar cycloaddition of hydroxylated pyrroline N-oxide nitrones with arynes can be a useful entry to analogues of bioactive natural products such as the codonopsinine and radicamine alkaloids 3 (Figure 1), according to the strategy outlined in Scheme 1. 4 Hydroxylated pyrroline N-oxides are a class of compounds readily achievable from natural sources through straightforward high yielding procedures. 5 In our group, 3,4-dialkoxy pyrroline N-oxides have been widely used in the synthesis of bioactive pyrrolidine, pyrrolizidine, and indolizidine heterocycles.…”

Transition-Metal-Free Synthesis of Benzo-Fused Five- and Six-Membered Heterocycles Employing Arynes

“…SCHEME 14 1,3-dipolar cycloaddition of α,β-unsaturated nitrones with arynes [37]. Very recently Khangarot and Kaliappan reported a 1,3-dipolar cycloaddition reaction of sugar-derived chiral nitrones 28 with arynes to synthesize the sugar-based benzo [d] isoxazolines with high-diasteroselectivity (Scheme 16) [39]. Recently, Larock and coworkers reported an efficient synthesis of benzisoxazolines by the 1,3-dipolar cycloaddition of nitrones with arynes generated from the Kobayashi precursor 1 using CsF in THF (Scheme 15) [38].…”

“…Nitrile oxides can be generated by the dehydrohalogenation of chlorooximes 31 under basic conditions. SCHEME 16 Synthesis of aza-C-aryl glycosides [39]. The research groups of Moses [40], Larock [41], and Browne [42] independently reported the efficient 1,3-dipolar cycloaddition reaction of in situ-generated nitrile oxides with arynes leading to the synthesis of benzisoxazoles.…”