Yb(OTf)3-promoted effective benzylation and allylation with N-tosyl amino group as a stable leaving group

Gold(III)-Catalyzed Propargylic Substitution Reaction Followed by Cycloisomerization for Synthesis of Poly-Substituted Furans from N-Tosylpropargyl Amines with 1,3-Dicarbonyl Compounds

“…In the initial propargylic substitution reaction, a hydroxyl, ether, or acetoxy group in the propargylic derivative serves as a leaving group and the reaction proceeds smoothly via the cleavage of the C-O bond to afford propargylic substitution products, which undergo cycloisomerization to yield furans. However, there are few examples of substitution reactions with nucleophiles using nitrogen leaving groups via C-N bond cleavage [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], and even fewer examples of propargylic substitution reactions of propargylic amines with active methylene compounds to obtain poly-substituted furans ( Scheme 1 , route b) [ 22 ]. The reason why there are few examples of reactions via C-N bond cleavage is presumably that nitrogen functional groups have inherently low leaving ability, and in addition, the preparation of nitrogen functional groups from other functional groups is cumbersome.…”

“…We considered that poly-substituted furans might be synthesized with a propargylic substitution reaction using the NHTs group of N -tosylpropargyl amine as a leaving group [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ], followed by cycloisomerization, based on the strategic use of a gold catalyst ( Scheme 2 ). Investigating the reported examples of substitution reactions using nitrogen leaving groups, it was predicted that nitrogen functional groups bearing the tosyl group as a protecting group would have sufficient leaving ability [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”

A Facile Iron‐Catalyzed Coupling of N‐Activated Benzyl Amines with 1,3‐Dicarbonyl Compounds through C‐N Bond Cleavage

“…reported that ZnCl 2 ‐TMSCl, a double Lewis acid catalyst system, can catalyze the substitution of amino groups from N‐ activated benzyl amines . Afterward, the use of Yb(OTf) 3 , as an exclusive Lewis acid catalyst, for the benzylation of 1,3‐dicarbonyl compounds was established by Wang and his group (Scheme ) . The use of moisture sensitive TMSCl or expensive Yb(OTf) 3 limits the practical utility of the existing methods.…”

Discovery of AZD8165 – a clinical candidate from a novel series of neutral thrombin inhibitors

“…3,4 Strategies to increase bioavailability by reducing basicity resulting in for example the 2-(amidinoaminooxy)ethyl and benzamidrazone moieties has been unsuccessful and permeability and bioavailability are still low for compounds containing these very polar moieties. 5,6 Attempts to increase bioavailability by increasing lipophilicity has resulted in issues like low solubility, high plasma protein binding and extensive metabolism. [7][8][9][10][11] Furthermore, the hydrophilic active agents (melagatran and dabigatran) have predominantly renal excretion.…”