Synthesis of Allenes by Isomerization Reactions

Exploring the Versatility of the Covalent Thiol–Alkyne Reaction with Substituted Propargyl Warheads: A Deciding Role for the Cysteine Protease

“…However, it was not possible to exclude the possibility that nucleophilic addition actually occurs with a more reactive allenic isomer, present at the enzyme active site in equilibrium with the unreactive terminal alkyne (Scheme 1C). 34,35 Alternatively, Arkona et al 32 propose an enzymetemplated stepwise reaction with stabilization of a secondary carbanion intermediate in the oxyanion hole to overcome the thermodynamically unfavored bond formation (Scheme 1D). This stepwise reaction mechanism would be similar to cysteine/ serine protease-mediated proteolysis of native amide bonds that involves stabilization of the anion intermediate in the oxyanion hole via interactions with polar residues such as glutamine or by H-bonds with backbone amides.…”

“…A radical-mediated thiol–yne mechanism was quickly excluded because covalent adduct formation was not prevented by absence of light and/or addition of radical scavengers and would have resulted in the anti-Markovnikov-type thiovinyl bond adduct with terminal C1 carbon (Scheme A). , Ekkebus et al and Sommer et al both propose a proximity-driven in situ thiol­(ate)–alkyne addition that involves direct nucleophilic attack of the catalytic cysteine thiol­(ate) to the alkyne internal C2 carbon (Scheme B). However, it was not possible to exclude the possibility that nucleophilic addition actually occurs with a more reactive allenic isomer, present at the enzyme active site in equilibrium with the unreactive terminal alkyne (Scheme C). , Alternatively, Arkona et al propose an enzyme-templated stepwise reaction with stabilization of a secondary carbanion intermediate in the oxyanion hole to overcome the thermodynamically unfavored bond formation (Scheme D). This stepwise reaction mechanism would be similar to cysteine/serine protease-mediated proteolysis of native amide bonds that involves stabilization of the anion intermediate in the oxyanion hole via interactions with polar residues such as glutamine or by H-bonds with backbone amides. , …”

Bifunctionalized Allenes. Part XIII. A Convenient and Efficient Method for Regioselective Synthesis of Phosphorylated α-Hydroxyallenes with Protected and Unprotected Hydroxy Group

“…In addition there are methods [50,51,52,53] for the synthesis of phosphorus-containing allenes (phosphonates [54,55,56,57,58,59], phosphinates [60,61], and phosphine oxides [62,63,64,65,66,67,68,69]) including reactions of α-alkynols with chloride-containing derivatives of phosphorus acids followed by [2,3]-sigmatropic rearrangement. Several diethylphosphono-substituted α-allenic alcohols were prepared by Brel [70,71] directly from alcohols by Horner-Mark rearrangement of unstable propargylic phosphites.…”

Microwave-Assisted Domino Access to C2-Chain Functionalized Furans from Tertiary Propargyl Vinyl Ethers

“…The [3,3]-Claisen rearrangement of propargyl vinyl ethers 1 (PVEs) constitutes a synthetically convenient route to substituted β-allenals 2 (eq ), which have proven to be suitable reactive units for the synthesis of important heterocycle cores. , In the presence of metallic catalysts, these intermediates have been selectively transformed into furans, − pyrroles, 2 H -pyrans, dihydropyrans, or 1,2-dihydropyridines. , Recently, we have shown how the microwave irradiation of PVEs constitutes an alternative manner to obtain these reactive intermediates in the absence of metals and how these intermediates can be efficiently transformed into substituted salicylaldehyde derivatives, 1,2-dihydropyridines, or pyridines via selective microwave-assisted (MWA) domino chemistry. Tertiary PVEs 3 (Scheme ), armed with an electron-withdrawing group (EWG) (amide or ester) at the tertiary propargylic position, constitute interesting building blocks with an unexplored synthetic potential. These units can be conveniently prepared by the triethylamine-catalyzed ABB′ three-component reaction (ABB′ 3CR) of alkyl propiolates and 1,2-ketoesters or 1,2-ketoamides or by treatment of the corresponding tertiary propargyl alcohol with alkyl propiolate in the presence of triethylamine .…”