Direct Synthesis of α‐Amino Acid Derivatives by Hydrative Amination of Alkynes

Abstract

α‐Amino acid derivatives are key components of the molecules of life. The synthesis of α‐amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we report a practical method for the preparation of α‐amino acid derivatives via direct hydrative amination of activated alkynes under mild conditions, relying on sulfinamides as the nitrogen source. Computational studies suggest that the reaction is enabled by a new type of sulfonium [2,3]‐sigmatropic rearrangement.

Construction of alkynyl and acyl disulfides directly through thiol-modification withN-alkynylthio phthalimides under acid catalysis

“…In contrast, the transformation of 3a to 4a proceeded readily (eqn (3)) under standard conditions, indicating that the hydrative oxyarylation had obvious structural selectivity. Based on these experimental results and literature reports, 8 a plausible reaction mechanism is proposed in Scheme 4b. Initially, the catalytic TFA promoted the release of the alkynylthio electrophile to form alkynyl disulfide 3 through S N 2 type S–S bond formation.…”

“…Although the hydrative oxyarylation for accessing acyl sulfides has achieved much progress, 8 the preparation of sulfur-tethered alkynes is still an unignorable limitation for the [3,3]-sigmatropic rearrangement. 12 Based on the successful synthesis of alkyne disulfides, it was expected that the acyl disulfide could be formed directly from the corresponding thiols via S–S bond formation and subsequent [3,3]-sigmatropic rearrangement.…”

“…Furthermore, relying on the exceptional electron-rich property and σ–π hyperconjugative effect of sulfur, hydrative oxyarylation of S-attached alkynes easily occurred through a sulfonium [3,3]-sigmatropic rearrangement for acyl disulfide formation (Scheme 1c). 8 Reports on irreversible thiol-modification through S–C bond formation inspired us to explore if functionalization of disulfides with alkynyl or acyl groups could be feasible through S–S bond formation (Scheme 1d): with the phthalimide-masked alkynylthio precursors, 9 the alkynyl disulfides could be rapidly and chemoselectively constructed from thiols; moreover, in the presence of sulfoxides, alkynyl disulfides could directly undergo the [3,3]-sigmatropic rearrangement. Herein, with the continuous exploitation of the design and construction of functionalized disulfides, 10 we would like to describe a new methodology for alkynyl and acyl disulfides through catalytic S–S bond formation and consequent [3,3]-sigmatropic rearrangement.…”

Silver(i)-catalyzed stereoselective Meyer–Schuster-type rearrangement: synthesis of densely substituted α-iodo α,β-unsaturated thioesters

“…In the second step, the ketenethionium intermediate B would readily react with the silver-activated N -iodosuccinimide 22 to afford the iodinated ketenethionium intermediate C . The energetic barrier for the nucleophilic attack of the hydroxyl group on the carbocation should be low 18 a ,23 and would then result in the oxetane intermediate D, which 24 after deprotonation by the silver succinate (forming E ) undergoes ring-opening via cleavage of the C–O bond, thus delivering the final α-iodo α,β-unsaturated thioester product and returning the silver( i ) catalyst.…”

Synthesis of Polypeptides and Poly(α-hydroxy esters) from Aldehydes Using Strecker Synthesis

“…These functional groups can also be further derivatized to yield biodegradable polymeric prodrugs, conjugates, and potential candidates for use as scaffolds in tissue engineering by cross-linking the polymer chains with these functional groups. In recent years, there has been an intensive effort to expand the versatility of “PLA-like” polyesters and polypeptides by synthesizing new derivatives of α-hydroxy acids and α-amino acids. − Some research groups have synthesized new classes of polyesters from hydroxylated amino acids. ,− For instance, Deng et al employed lignocellulosic biomass-derived α-hydroxyl acids to produce α-amino acids, including alanine, leucine, valine, aspartic acid, and phenylalanine employing Ruthenium nanoparticles supported on carbon nanotubes (Ru/CNT) as catalyst . Initially, these hydroxylated amino acids were synthesized from nonpolar amino acids such as phenylalanine and polymerized into a new class of aliphatic polyesters.…”