An Alkynyliodide Cycloaddition Strategy for the Construction of Iodoisoxazoles

Abstract

The thermally promoted cycloaddition between alkynyliodides and nitrile oxides is reported. The process offers excellent regioselectivity and a broad scope with respect to both the iodoalkynes and chloro-oximes. Further functionalization of the highly decorated iodoisoxazole motifs can be achieved via Suzuki cross-coupling.

β‐Cyclodextrin–Glycerol Dimers: Synthesis and NMR Conformational Analysis

“…The 4‐aluminoisoxazoles can be intercepted with a variety of electrophiles (NCS, NIS, RN=CO, nitrile oxides) to produce trisubstituted isoxazoles. In 2010, Browne demonstrated the synthesis of 4‐iodoisoxazoles utilizing iodoalkynes in the thermally promoted [3+2] cycloaddition with nitrile oxides (Scheme D) 24. The reaction was accomplished in a short reaction time (DME, 120 °C, 20 min).…”

“… Synthesis of isoxazoles via thermal 1,3‐dipolar cycloaddition using silicon‐, MIDA‐, aluminum‐ and iodine‐substituted alkynes. A: Denmark;20 B: Grob;22 C: Micouin;23 D: Browne 24…”

Microwave‐Assisted Metal‐Free Decarboxylative Iodination/Bromination of Isoxazole‐4‐carboxylic Acids

“…Finally, we considered investigating the reaction under microwave irradiation and we were pleased to discover that the 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 reaction was completed in 15.0 min to afford 3 caa in 95% yield (entry 14). Alternatively, identical reaction performed in MeCN as the medium produced 3 caa in 87% yield whereas replacing NIS with I 2 (3.0 equiv) as the iodine source gave 3 caa in 88% yield under microwave irradiation (entries [15][16]. Thus the condition for decarboxylative iodination to obtain best yield of 3 caa was reacting 2 ca (1.0 equiv) with NIS (4.0 equiv) and K 3 PO 4 (1.0 equiv) in 1,4-dioxane under microwave irradiation at 150°C for 15 min.…”

“…[15] Browne et al developed the synthesis of 4-iodoisoxazole from alkynyliodide generated from the copper ylide. [16] NIS. [17] More recently, Hu et al disclosed the route to 3-chloro-4iodoisoxazoles that involved the reaction of dichloroformaldoxime and copper (I) alkyne in the presence of molecular iodine.…”

Ruthenium‐Catalyzed Cycloadditions of 1‐Haloalkynes with Nitrile Oxides and Organic Azides: Synthesis of 4‐Haloisoxazoles and 5‐Halotriazoles

“…However, examples of high‐yielding reactions involving 1‐haloalkynes and nitrile oxides remain remarkably scarce 29. For example, thermal cycloadditions of nitrile oxides and 1‐haloalkynes often either require alkynes substituted with highly activated hypervalent iodine species30 or a large excess of one of the reactants29c and/or controlled addition of the nitrile oxide component 29b. Despite these precautions, these reactions still often result in mixtures of regioisomers with low to moderate yields 16a.…”