Ryu Sakamoto

Stereocontrolled Synthesis of Vicinal Diamines by Organocatalytic Asymmetric Mannich Reaction of N-Protected Aminoacetaldehydes: Formal Synthesis of (−)-Agelastatin A

The 1,2-diamine (vicinal diamine) motif is present in a number of natural products with interesting biological activity and in many chiral molecular catalysts. The efficient and stereocontrolled synthesis of enantioenriched vicinal diamines is still a challenge to modern chemical methodology. We report here both syn- and anti-selective asymmetric direct Mannich reactions of N-protected aminoacetaldehydes with N-Boc-protected imines catalyzed by proline and the axially chiral amino sulfonamide (S)-3. This organocatalytic process represents the first example of a Mannich reaction using Z- or Boc-protected aminoacetaldehyde as a new entry of α-nitrogen functionalized aldehyde nucleophile in enamine catalysis. The obtained optically active vicinal diamines are useful chiral synthons as exemplified by the formal synthesis of (-)-agelastatin A.

Diastereoselective Radical Hydroacylation of Alkylidenemalonates with Aliphatic Aldehydes Initiated by Photolysis of Hypervalent Iodine(III) Reagents

Diastereoselective radical hydroacylation of chiral alkylidenemalonates with aliphatic aldehydes is realized by the combination of a hypervalent iodine(III) reagent and UV-light irradiation. The reaction is initiated by the photolysis of hypervalent iodine(III) reagents under mild, metal-free conditions, and is the first example of diastereoselective addition of acyl radicals to olefins to afford chiral ketones in a highly stereoselective fashion. The obtained optically active ketones are useful chiral synthons, as exemplified by the short formal synthesis of (-)-methyleneolactocin.

Catalytic asymmetric synthesis of cyclic amino acids and alkaloid derivatives: application to (+)-dihydropinidine and Selfotel synthesis

An asymmetric synthesis of cyclic amino acids having piperidine and azepane core structures was realized starting from readily available glycine and alanine esters by combination of phase-transfer catalyzed asymmetric alkylation and subsequent reductive amination. Some of these key intermediates were successfully transformed to natural alkaloid dihydropinidine and N-methyl-D-aspartate (NMDA) antagonist Selfotel.

Amine-catalyzed asymmetric cross-aldol reactions using heterofunctionalized acetaldehydes as nucleophiles.

Various heterofunctionalized acetaldehydes were successfully employed in an amine-catalyzed asymmetric cross-aldol reaction, affording a variety of synthetically useful 1,2-difunctionalized compounds such as 1,2-diols and 1,2-aminoalcohols. With this method, both syn- and anti-1,2-difunctionalized compounds were obtained from the same set of reactants by using the appropriate amine catalyst.

The Direct C–H Difluoromethylation of Heteroarenes Based on the Photolysis of Hypervalent Iodine(III) Reagents That Contain Difluoroacetoxy Ligands

In this letter, an efficient method for the photolytic generation of difluoromethyl radicals from [bis(difluoroacetoxy)iodo]benzene reagents is described. The present approach enables the introduction of difluoromethyl groups into various heteroarenes under mild conditions in the absence of any additional reagents or catalysts.

Synthesis of 3-mono-substituted binaphthyl-based secondary amine catalysts via monobromination of an axially chiral dicarboxylic acid derivative.

A facile synthetic route to a 3-bromo binaphthyl-based secondary amine through the monobromination of an axially chiral dicarboxylic acid derivative has been developed. The combination of this new procedure with coupling reactions established an efficient synthetic approach to a series of binaphthyl-based secondary amine catalysts containing various functional groups in an efficient way.

A Synthetic Route to Sodium α-Aminoalkanesulfinates and Their Application in the Generation of α-Aminoalkyl Radicals for Radical Addition Reactions

The synthesis of sodium α-aminoalkanesulfinates and their synthetic utility as α-aminoalkyl radical precursors are reported. A variety of α-aminoalkanesulfinates were readily obtained from the reaction between the anions of N-Boc-protected alkylamines and 1,4-diazabicyclo[2.2.2]octanebis(sulfur dioxide). Treatment of sodium α-aminoalkanesulfinates with (diacetoxyiodo)benzene easily generated the corresponding α-aminoalkyl radicals under mild conditions, which were then applied in radical 1,2-addition to imines, radical 1,4-addition to electron-deficient olefins, and radical addition/cyclization to 2-isocyanobiphenyls.

Copper-Catalyzed C(sp)–C(sp3) Coupling of Terminal Alkynes with Alkylsilyl Peroxides via a Radical Mechanism

A copper-catalyzed C(sp)-C(sp3) coupling reaction between terminal alkynes and alkylsilyl peroxides is reported. In the presence of a copper catalyst and 4-dimethylaminopyridine, the reaction smoothly affords a variety of internal alkynes by coupling alkylsilyl peroxides and terminal alkynes. Mechanistic studies suggest that the reaction proceeds via a radical mechanism, whereby the alkyl radicals are generated from the alkylsilyl peroxides. The present transformation represents a rare example of a radical-mediated C(sp)-C(sp3) coupling reaction of terminal alkynes.

Alkylsilyl Peroxides as Alkylating Agents in the Copper‐Catalyzed Selective Mono‐N‐Alkylation of Primary Amides and Arylamines

The copper-catalyzed selective mono-N-alkylation of primary amides or arylamines using alkylsilyl peroxides as alkylating agents is reported. The reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with respect to the alkylsilyl peroxides, as well as to the primary amides and arylamines. Mechanistic studies suggest that the present reaction should proceed through a free-radical process that includes alkyl radicals generated from the alkylsilyl peroxides.