Unexpected lateral-lithiation-induced alkylative ring opening of tetrahydrofurans in deep eutectic solvents: synthesis of functionalised primary alcohols

Abstract

o-Tolyl-substituted tetrahydrofurans undergo highly regioselective ring opening with the concomitant formation of new C-C bonds as the result of a lateral lithiation reaction. This reaction provides a new method for the synthesis of functionalised primary alcohols and can be run directly in protic eutectic mixtures as benign reaction media at 0 °C and under air, competitively with protonolysis.

Eine wasserhaltige Organokaliumverbindung basierend auf Bis(4,6‐tert‐Butylbenzoxazol‐2‐yl)methanid und ihre unerwartete Hydrolysebeständigkeit

“…Die Ergebnisse ließen die Schlussfolgerung zu, dass der vorliegende Lithium/Bromid-Austausch am Aromaten mindestens genauso schnell, wenn nicht sogar schneller vonstattengeht als eine konkurrierende Zersetzungsreaktion zu BuT und LiOT. [12][13][14][15][16][17][18] Darüber hinaus haben DESs eine weitreichende Anwendung in Form effektiver Elektrolytlçsungen fürS olarzellen sowie in der Biokatalyse und als Reaktionsmedium photosynthetischer Reaktionszentren im Bereich der Energietechnologie gefunden. Im Gegensatz dazu führten Versuche ohne Wasser zur signifikanten Verringerung beider Werte.…”

Reactivity of Polar Organometallic Compounds in Unconventional Reaction Media: Challenges and Opportunities

“…o ‐Tolyl‐substituted tetrahydrofuran derivatives 16‐H have recently been found to undergo an unprecedented highly regioselective intramolecular C–O bond‐breaking reaction, triggered by the corresponding benzylically lithiated intermediates 16‐Li , ending up with the formation of functionalised primary alcohols 17 featuring incorporation in their skeletons both of a second equivalent of base and of an electrophile (if any) at a tertiary carbon atom (Scheme ) 24…”

“…As a general reaction procedure, a commercial hydrocarbon solution of the organolithium compound ( s BuLi, i PrLi, t BuLi) was added by rapidly spreading it out over a mixture of 16‐H in CPME and ChCl/Gly (1:2), at 0 °C, under air, and with vigorous stirring, and quenched with the electrophile after a 3 min reaction time to give alcohols 17 in yields up to >98 %. The scope, limitation and mechanistic aspects of this reaction, which pioneers “greener” alkylative THF ring‐opening processes, have been discussed 24. Interestingly, s BuLi was found to promote faster deprotonation than t BuLi, and ortho ‐lithiation seriously competes with benzylic lithiation only in the case of substrates possessing an ethyl group in an ortho position at one of the two aromatic rings.…”

Na@SiO2-Mediated Addition of Organohalides to Carbonyl Compounds for the Formation of Alcohols and Epoxides

“…Capriati et al 101112 applied the Barbier–Grignard type reactions to the synthesis of substituted tetrahydrofurans from γ-haloketones. The same research group explored the lithium-induced alkylative ring opening of tetrahydrofurans, which leads to the synthesis of primary alcohols1213.…”