A new versatile linker for the solid-phase synthesis of secondary amines

N-Alkylation Reactions and Indirect Formation of Amino Functionalities in Solid-Phase Synthesis

“…267 DEAD-PPh 3 and DEAD-PEt 3 proved to be efficient for the alkylation of sulfonamide-activated resin-bound diamines, and the DEAD-PPh 3 combination was superior for the alkylation of resin-bound N-nosylglycine. 267 In addition to the Mitsunobu alkylations of the sulfonamides discussed above, the reaction of other activated nitrogen species, such as 4-nitrobenzenesulfonamides (65-99% conversion), 268 guanidines (~17-95% yields), 269,270 dioxotriazines (58-78% yields), 271 dialkyl iminodicarbonates (33-85% yields), 272 and phthalimides (8-49% yields) 273 as well as purines (microwave-assisted, 45-59% yields) 274 and ammonium iodides (66-97% yields) 275 have been performed.…”

Access to Secondary Amines through Hydrogen Autotransfer Reaction Mediated by KOtBu

“… [3] Although several methods are available in the literature, for synthesizing alkyl‐amines including reductive methods, [4] carbon–nitrogen cross‐coupling reactions, [5] N ‐alkylation with an alkyl halide, [6] etc. most of these reports suffer from drawbacks such as long and tedious reaction protocol, [7] requirement of expensive alkyl halides as alkylating agents, [8] generations of the stoichiometric amount of waste, [9] low atom efficiency, [10] narrow substrate scope, [11] and over alkylation [12] . To avoid over‐alkylation, a route via imine followed by hydrogenation is well appreciated for a long time.…”

Development of an Indole Safety-Catch Linker Using Analytical Constructs

“…Solid-phase organic synthesis has become widely accepted for the preparation of combinatorial libraries and compound arrays to accelerate hit discovery and lead optimization processes. − The use of the solid phase allows simple separation of resin-bound products from solution-phase reagents; the ability to drive reactions to completion by using excesses of reagents in high concentration; and the generation of synthetic protocols that are unhindered by the physical characteristics of each individual library member, thus facilitating the automation of the process. The growing complexity of chemistry being performed on the solid phase requires the continuous development of suitable linker molecules with the desired properties. − …”

“…The growing complexity of chemistry being performed on the solid phase requires the continuous development of suitable linker molecules with the desired properties. [5][6][7][8] The safety-catch principle, as applied to linkers, 5,6 involves the conversion of a relatively stable, "inactivated" form of the linker into a labile, isolable, and cleavable entity. 9 An advantage of safety-catch linkers is their ability to tolerate harsh or otherwise incompatible reaction conditions through an entire reaction sequence and then, after removal of the safety catch, to release the desired product into solution under mild conditions or in such a way as not to require further purification.…”