Synthesis of new tetrazolyl derivatives of L- and D-phenylalanine

Catalytic Direct Regioselective Synthesis of Phosphonylated Tetrazoles from Aryl Diazonium Salts and Seyferth-Gilbert Reagent

“…The alteration on phosphonate group is accommodated well and provided tetrazole 3ad in 85% yield. Furthermore, phenylalanine-derived diazonium salt underwent the cycloaddition under identical conditions and gave tetrazolic amino acid 3ae in 79% yield, which may offer potential biorthogonal chemical handles for fluorescent labeling . The accurate structures of these phosphonylated tetrazoles are assigned by analogy based on X-ray analysis of compound 3x . , …”

“…Subsequently, a gram-scale experiment was conducted and afforded compound 3e in a comparable yield of 88% (Scheme a) . The tetrazole core can undergo photoinduced DPC reaction with different dipolarophiles, as demonstrated by the formation phosphonylated pyrazoline 5 and pyrazole 6 in 83% and 74% yield, respectively (Scheme b) . Furthermore, by using the newly developed cycloaddition protocol, a phosphonylated analogue of P2X3 receptor antagonist was rapidly prepared from aromatic amine 7 with moderate total yield (Scheme c) …”

Construction of Difluoromethylated Tetrazoles via Silver-Catalyzed Regioselective [3 + 2] Cycloadditions of Aryl Diazonium Salts

“…Significantly, this silver-catalyzed one-pot diazotization/cycloaddition sequence is also amenable for the late-stage modification of biologically interesting compounds, as exemplified by the liberation of structurally complex molecular 2k′, which is derivatized from tocopherol accordingly. 14 The practicality of this protocol is demonstrated by a gramscale preparation of 2a and 2s in isolated yields of 78% and 84%, respectively (Scheme 4a). Meanwhile, the difluoromethylated tetrazole 2v could also be obtained in 75% yield through the one-pot diazotization/cycloaddition sequence from 4chloroaniline directly on a 5.0 mmol scale (Scheme 4a).…”

“…Substrates with an unprotected hydroxyl or carboxyl group proceeded much more smoothly to give the corresponding cycloadducts 2h′ – 2j′ (72–80% yields) than the preceding two-step protocol (lower than 10% yields). Significantly, this silver-catalyzed one-pot diazotization/cycloaddition sequence is also amenable for the late-stage modification of biologically interesting compounds, as exemplified by the liberation of structurally complex molecular 2k′ , which is derivatized from tocopherol accordingly …”