Dehydrative Fragmentation of 5-Hydroxyalkyl-1H-tetrazoles: A Mild Route to Alkylidenecarbenes

Abstract

The development of a mild, base-free method for the generation of alkylidenecarbenes is reported. Treatment of 5-hydroxyalkyl-1 H-tetrazoles with carbodiimides generates products arising from the 1,2-rearrangement or [1,5]-C-H bond insertion of a putative alkylidenecarbene. Formation of this divalent intermediate is proposed to occur by way of a tetraazafulvene, which undergoes extrusion of two moles of dinitrogen. Details of this methodology, its applicationtothesynthesisofcombretastatinA-4andanimprovedrouteto5-hydroxyalkyl-1 H-tetrazolesare described.

A Versatile and Efficient Palladium–meta‐Terarylphosphine Catalyst for the Copper‐Free Sonogashira Coupling of (Hetero‐)Aryl Chlorides and Alkynes

“…13 C NMR (151 MHz, CDCl 3 ): δ = 160.17, 133.61, 132.00, 129.84, 128.86, 128.48, 124.15, 115.94, 89.93, 88.63, 55.85 ppm. The spectroscopic data matched that previously reported 24…”

“…1 The spectroscopic data matched that previously reported. [24] 3-(Phenylethynyl)pyridine (3e): Following general method A, 3chloropyridine (114 mg, 1 mmol) and phenylacetylene (2a; 123 mg, 1.2 mmol) afforded the title compound as a yellow oil (168 mg, 94 %) by using hexane/EtOAc (10:1) as the column eluent. 1 H NMR (600 MHz, CDCl 3 ): δ = 8.76 (dd, J = 2.2, 1.0 Hz, 1 H), 8.52 (dd, J = 4.9, 1.7 Hz, 1 H), 7.77 (dt, J = 7.9, 1.9 Hz, 1 H), 7.65-7.44 (m, 2 H), 7.42-7.27 (m, 3 H), 7.24 (ddd, J = 7.9, 4.9, 0.9 Hz, 1 H) ppm.…”

Recent advances in alkylidene carbene chemistry

“…40 Wardrop has also reported the generation of alkylidene carbenes via tetraazafulvenes 45, accessing them through dehydration of 5-hydroxy-1H-tetrazoles 54 with carbodiimides (Scheme 20). 41 The 5-hydroxyalkyl-1H-tetrazoles 54 were readily prepared in two steps from precursor carbonyl compounds via addition of 1-allyl-5-tetrazoyllithium 55 followed by Ni-catalyzed N-deallylation in the presence of t BuMgCl (Scheme 21). A range of substrates were prepared this way, mostly in good yields.…”

“…Wardrop applied his tetraazafulvene methodology in a total synthesis of combretastatin A4 (Scheme 106). 41 Tykwinski's demonstration that alkynyl groups undergo 1,2-migrations (Scheme 27) 47,48,131 has led to significant developments in the synthesis of polyynes, and has been utilized in investigations into the potential structure and properties of the proposed carbon allotrope carbyne. 49 The insertion of alkylidene carbenes into carbonecarbon double bonds has proven to be a useful tool in the synthesis of complex natural product frameworks.…”

Lewis Acid Mediated Fragmentation of Tetrazoles towards Triazoles

“…[2] The fragmentation of substituted tetrazoles does not usually occur under 250°C. [3] Besides these triazole formations, high-yielding fragmentations of tetrazoles have been scarcely disclosed: in a few oxidative fragmentations, [4] in water elimination from diphenylcarbinol derivatives, [5] and in a few UV irradiation reactions. [3] Besides these triazole formations, high-yielding fragmentations of tetrazoles have been scarcely disclosed: in a few oxidative fragmentations, [4] in water elimination from diphenylcarbinol derivatives, [5] and in a few UV irradiation reactions.…”