s-Block cooperative catalysis : alkali metal magnesiate-catalysed cyclisation of alkynols

Fairley, Michael and Davin, Laia and Hernan-Gomez, Alberto and García-Álvarez, Joaquín and O'Hara, Charles T. and Hevia, Eva (2019) s-Block cooperative catalysis : alkali metal magnesiate-catalysed cyclisation of alkynols. Chemical Science, 10 (22). pp. 5821-5831. ISSN 2041-6520 (https://doi.org/10.1039/C9SC01598A)

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Mixed s-block metal organometallic reagents have been successfully utilised in the catalytic intramolecular hydroalkoxylation of alkynols. This success has been attributed to the unique manner in which these reagents can overcome the challenges of the reaction: namely OH activation and coordination to and then addition across a C≡C bond. In order to optimise the reaction conditions and to garner vital catalytic system requirements, a series of alkali metal magnesiates were enlisted for the catalytic intramolecular hydroalkoxylation of 4-pentynol. In a prelude to the main investigation, the homometallic magnesium dialkyl reagent MgR2 (where R = CH2SiMe3) was utilised. This reagent was unsuccessful in cyclising the alcohol into 2-methylenetetrahydrofuran 2a or 5-methyl-2,3-dihydrofuran 2b, even in the presence of multidentate Lewis donor molecules such as N,N,N′,N′′,N′′-pentamethyldiethylenetriamine (PMDETA). Alkali metal magnesiates MIMgR3 (when MI = Li, Na or K) performed the cyclisation unsatisfactorily both in the absence/presence of N,N,N′,N′-tetramethylethylenediamine (TMEDA) or PMDETA. When higher-order magnesiates (i.e., MI2MgR4) were employed, in general a marked increase in yield was observed for MI = Na or K; however, the reactions were still sluggish with long reaction times (22–36 h). A major improvement in the catalytic activity of the magnesiates was observed when the crown ether molecule 15-crown-5 was combined with sodium magnesiate Na2MgR4(TMEDA)2 furnishing yields of 87% with 2a : 2b ratios of 95 : 5 after 5 h. Similar high yields of 88% with 2a : 2b ratios of 90 : 10 after 3 h were obtained combining 18-crown-6 with potassium magnesiate K2MgR4(PMDETA)2. Having optimised these systems, substrate scope was examined to probe the range and robustness of 18-crown-6/K2MgR4(PMDETA)2 as a catalyst. A wide series of alkynols, including terminal and internal alkynes which contain a variety of potentially reactive functional groups, were cyclised. In comparison to previously reported monometallic systems, bimetallic 18-crown-6/K2MgR4(PMDETA)2 displays enhanced reactivity towards internal alkynol-cyclisation. Kinetic studies revealed an inhibition effect of substrate on the catalysts via adduct formation and requiring dissociation prior to the rate limiting cyclisation step.


Fairley, Michael ORCID logoORCID: https://orcid.org/0000-0002-6021-0339, Davin, Laia ORCID logoORCID: https://orcid.org/0000-0002-7927-4930, Hernan-Gomez, Alberto, García-Álvarez, Joaquín, O'Hara, Charles T. and Hevia, Eva ORCID logoORCID: https://orcid.org/0000-0002-3998-7506;