Bio- and air-tolerant carbon–carbon bond formations via organometallic ruthenium catalysis

Abstract

Dedicated to Dr. Alfred Bader on the occasion of his 85th birthday in recognition of his outstanding contributions as a chemist, enterpreneur, and benefactor.Selected [2+2+2] cycloadditions, alkene-alkyne coupling and fusion of enyne with diazo compound, all triggered by an artificial organometallic ruthenium catalyst are demonstrated to proceed under ambient aerobic aqueous conditions in presence of bodily fluids or cell lysate. To the best of our knowledge, these are the first examples of bio-and air-tolerant C-C bond formation catalyzed by an artificial organometallic compound.

Organometallic catalysis in aqueous and biological environments: harnessing the power of metal carbenes

“…According to the authors, the reaction proceeds very quickly (5 min), in an open to air flask, and in the presence of complex biological media such as E. coli cell lysate, Rattus norvegicus urine, human serum or fetal bovine serum. 142 These results are very promising in terms of the bioorthogonal possibilities of this type of carbene transfer reactions.…”

Ruthenium-Catalyzed Cycloadditions to Form Five-, Six-, and Seven-Membered Rings

“… , Taking advantage of these electronic effects, Itoh and Yamamoto conducted [2+2+2] cycloadditions 1,6-diynes with chloroacetonitriles for the synthesis of C -arylribosides, and Kotora performed [2+2+2] cycloadditions of halogen-terminated 1,6-diynes with nitriles to form halopyridines (not shown) . Additional studies demonstrate that Cp*RuCl­(cod)-catalyzed [2+2+2] cycloadditions of 1,6-diynes with nitriles can be conducted in air, water and even fetal bovine serum (not shown) …”

“…282 Additional studies demonstrate that Cp*RuCl(cod)-catalyzed [2+2+2] cycloadditions of 1,6-diynes with nitriles can be conducted in air, 283 water 284 and even fetal bovine serum (not shown). 229 In 2017, using Cp*RuCl(cod) as a precatalyst, Goswami reported [2+2+2] cycloadditions of 1,6-diynes with Ncyanoindoles to form N-(2-pyridyl)indoles (Scheme 62). 285 The same year, Goswami reported related [2+2+2] cycloadditions of 1,6-diynes with 3-thiocyanatoindoles to form 3-(2thiopyridyl)indoles (Scheme 62).…”

“… Independent computational studies by Kirchner , and Saá on the mechanism of the parent Cp-ruthenium­(II)-catalyzed alkyne [2+2+2] cyclotrimerization corroborated the proposed oxidative coupling–alkyne insertion pathway. Cp*RuCl­(cod)-catalyzed crossed [2+2+2] cycloadditions of DMAD were studied further by Mitsudo, , Teplý, and Kotha, but low isomer selectivities were observed (not shown). A stunning application of Yamamoto’s crossed [2+2+2] cycloaddition of propargyl alcohols, alkynylboronate and terminal alkynes is found in Cramer’s total synthesis of the highly complex glycosylated paracyclophane natural product fijiolide A, which was reported in 2015 (Scheme ).…”

Ruthenium-catalyzed intermolecular [2+2+2] alkyne cyclotrimerization in aqueous media under microwave irradiation

“…However, efforts in this direction have been scarce and only a very limited number of efficient and selective catalysts in this medium have seen the light to date (43,44 Figure 1) (45) merits to be highlighted since, as recently described by us (46), it displays an outstanding performance in the intermolecular cyclization of both terminal and internal alkynes, and a wide tolerance to functional groups (47). In order to assess whether a change in the heating method (MW vs. thermal) could affect the course of these catalytic reactions, we decided to explore the behavior of complex 1 under MW irradiation.…”