Unexpected O–H Insertion of Rhodium-Azavinylcarbenes with N-Acylhydrazones: Divergent Synthesis of 3,6-Disubstituted- and 3,5,6-Trisubstituted-1,2,4-Triazines

Abstract

A practical and efficient method for divergent synthesis of 3,6-disubstituted- and 3,5,6-trisubstituted-1,2,4-triazines via unexpected rhodium-catalyzed O-H insertion/rearrangement/conditions-controlled intramolecular cyclization and oxidation reaction under mild conditions has been developed. Notably, it is the first example for the synthesis of 1,2,4-triazines with different substituted-patterns via a common intermediate with excellent chemoselectivities by the reaction of N-acylhydrazones as aze-[3C] or [4C] synthons with N-sulfonyl-1,2,3-triazoles as aze-[2C] synthons. Furthermore, this method allows direct access to di(het)aryl ketone frameworks containing 1,2,4-triazine moiety for the first time, serving as a versatile building block for the synthesis of other useful heterocyclic skeletons, such as pyridine or pyridazinone-fused triazine in excellent yields.

Pot, Atom, Step Economic (PASE) Approach towards (Aza)‐2,2′‐Bipyridines: Synthesis and Photophysical Studies

“…Some other approaches were also reported, such as the thermolysis of α‐azido ketone acylhydrazones, the interaction of iso‐ nitrosoacetophenones either with amidrazones in acidic conditions (in some cases the 1,2,4‐triazine‐4‐oxides are also formed), or with hydrazones of aldehydes . Few recent methods should be also mentioned, for example, the rhodium‐catalyzed cyclocondensation of aza vinylcarbenes with N ‐acylhydrazones, a synthesis based on 2‐chloro‐ N ‐(2‐(4‐chloro‐phenyl)‐2‐oxoethyl)‐propan‐amide, hydrohydrazination of propargylamides with BocNHNH 2 in presence of Zn(OTf) 2 and, finally, acid‐catalyzed ring‐opening / cyclization / oxidation of aziridines with N ‐tosylhydrazones …”

Rhodium(II)‐Catalyzed Reaction of 1‐Tosyl‐1,2,3‐triazoles with Morita–Baylis–Hillman Adducts: Synthesis of 3,4‐Fused Pyrroles

“…We have a great interest in azaheterocycle synthesis and N ‐sulfonyl‐1,2,3‐triazoles chemistry. We have reported a practical and efficient method for divergent synthesis of 3,6‐disubstituted‐ and 3,5,6‐trisubstituted‐1,2,4‐triazines via unexpected rhodium‐catalyzed O−H insertion/rearrangement/ conditions‐controlled intramolecular cyclization and oxidation reaction under mild conditions . Soon afterwards, a novel protocol for the synthesis of unsymmetrical indigo‐like ( E )‐α‐amino enaminones by rhodium catalyzed O−H insertion and subsequent rearrangement of isatins with 1‐tosyl‐1,2,3‐triazoles has also been reported by us .…”

“…Meng synthesis of 3,6-disubstituted-and 3,5,6-trisubstituted-1,2,4-triazines via unexpected rhodium-catalyzed OÀHi nsertion/rearrangement/c onditions-controlled intramolecular cyclization and oxidation reactionu nder mild conditions. [12] Soon afterwards, an ovel protocol for the synthesiso fu nsymmetrical indigo-like (E)-a-aminoe naminones by rhodiumc atalyzed OÀH insertiona nd subsequentr earrangement of isatins with 1tosyl-1,2,3-triazoles has also been reported by us. [13] Up to now, the direct O-H insertions of a-imino rhodium carbenoids with propers ubstrates, [14] taking benzylic alcohol [14e] for example, have been well studied.M oreover,s ome methods have been developed for the construction of nitrogen-containing heterocycles (such as pyrrole skeleton) based on OÀHi nsertion and subsequentr earrangement.…”

“…Solvent effect was then tested with DBU as the base (entry [8][9][10][11]. The results show that the nonpolar solventt oluene is the best choice.M oreover, the yield did not increase either at ah igher reaction temperature or a lower reaction temperature (entry [12][13][14].W e envisioned that the additional oxidants would promote the reaction. Therefore, oxidantsl ike DDQ or PIDA werea dded, but the desired product could not be obtained (entry [15][16].…”

“…Moreover, the use of 1,2-dichloroethane (DCE) or toluene as the solventd id not increase the yield of 3aa (entry [8][9]. The addition of Lewis acidh ave no positivee ffects (entry [10][11][12][13][14]. Finally, the reaction of MBH adduct 1a with 1.2 equiv of triazole 2a catalyzed by Rh 2 (Oct) 4 in CHCl 3 at 75 8Cw ere set as the optimum reaction conditions.…”