Kazuhito Hioki

Formation of carboxamides by direct condensation of carboxylic acids and amines in alcohols using a new alcohol- and water-soluble condensing agent: DMT-MM

Abstract Selective formation of carboxamides in an alcohol or water by an exceptionally convenient one-step procedure in which a condensing agent is simply added to a mixture of acids and amines has been achieved successfully by using a new condensing agent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). Activation of carboxylic acids by DMT-MM in the presence of amines and subsequent aminolysis of the resulting acyloxytriazine in alcoholic solvents occurred selectively and led to the formation of carboxamides in excellent yields. The rate of aminolysis of the acyloxytriazine intermediate can be estimated to be about 2×10 4 times greater than that of methanolysis. The amide/ester selectivity observed using DMT-MM was much larger than that obtained with DCC or EDC. Condensation of polar substrates, such as amino acid esters and their hydrochlorides, glucosamine hydrochloride, sodium acetate and dicarboxylic acids, proceeded successfully in MeOH, water or aqueous MeOH in good yields. The present reaction is technically quite simple and easy to achieve. It proceeds by simple mixing of acids, amines and DMT-MM without any additives, and the MeOH is readily removable by a rotary evaporator after completion of the reaction.

Approach to green chemistry of DMT-MM: recovery and recycle of coproduct to chloromethane-free DMT-MM

Abstract A simple procedure for the isolation of 2-hydroxy-4,6-dimethoxy-1,3,5-triazine (HO-DMT), a coproduct arising from dehydrating condensation using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) has been established. HO-DMT can be recycled by treatment with POCl 3 to give 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT), which is further converted to DMT-MM. Alternatively, reaction with triflic anhydride followed by addition of N -methylmorpholine gives DMT-MM triflate.

Alkylidenecarbenes from 1,1-dihalogenoalkenes with samarium diiodide: Mild and efficient method for the synthesis of cyclopentenes

A new mild method for construction of cyclopentenes via 1,5-CH insertion of alkylidenecarbenes by the reaction of 2,2-dialkyl-1,1-dihalogenoalkenes with SmI2 in benzene—hexamethylphosphoric triamide (HMPA) was developed.

Substrate-Selective Dehydrocondensation at the Interface of Micelles and Emulsions of Common Surfactants†

The utilization of micelles for controlling organic reactions has been attracting considerable attention. The micellar interface is well known as an excellent reaction field for hydrolysis. In spite of this fact, the reverse reaction, that is, the dehydrocondensation of a carboxylic acid and an amine, can also be accelerated at the micellar interface. In fact, we successfully showed that a remarkable rate acceleration for the reaction of aliphatic carboxylic acids (A) and amines (B) by 1,3,5-triazine-based amphiphilic dehydrocondensing agents (C), which are available in water similar to 4-(4,6dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), 7] occurred up to 2000 times faster in micelles than in a normal homogeneous molecular dispersion phase (Figure 1). Because both carboxylic acids and amines

Convenient modular method for affinity labeling (MoAL method) based on a catalytic amidation

A modular methodology for affinity labeling, in which three essential elements generally constituting affinity probes are prepared separately as individual molecules, has been developed based on a catalytic amidation.

Generation and Reactions of Alkynylsamariums

Abstract Three methods have been developed for generating alkynylsamariums: (1) reduction of iodoalkynes with SmI 2 in the presence of HMPA, (2) deprotonation at the terminal position of 1-alkynes either by tetrahydrofurylsamarium generated by PhI and SmI 2 in THF, or, (3) deprotonation by butyllithium followed by metal–metal exchange with SmI 3 . Alkynylsamariums arising from iodoalkynes with SmI 2 undergo coupling with carbonyl compounds under both Barbier and Grignard conditions in benzene-HMPA or THF-HMPA as a solvent system. Tetrahydrofurylsamarium generated from iodobenzene and SmI 2 in THF can deprotonate from terminal alkynes to yield alkynylsamariums whereas other alkylsamariums, such as ethyl-, isopropyl-, cyclohexyl-, and cyclopentylsamarium do not work well. Metal–metal exchange between an alkynyllithium and SmI 3 is also effective; the reactive species in this case would be alkynylsamariums rather than alkynyllithiums. To reveal the properties of alkynylsamariums, we examined the stability and reactivity of alkynylsamariums toward various electrophiles.

Generation of alkylidenecarbenes from 1,1-dibromoalk-1-enes by the reaction with samarium diiodide in hexamethylphosphoric triamide-benzene

Reaction of 1,1-dibromoalk-1-enes with samarium diiodide in benzene containing 10% of hexamethylphosphoric triamide (HMPA) affords rearranged alkynes; generation of alkylidenecarbenes is probably involved.

SMI2-MEDIATED COUPLING REACTIONS BETWEEN IODOALKYNES AND KETONES OR ALDEHYDES TO GIVE PROPARGYL ALCOHOLS

Abstract Samarium iodide (SmI 2 ) mediates a coupling reaction between alkynyl iodides and ketones or aldehydes to give propargyl alcohols in the presence of hexamethylphosphoric triamide (HMPA) in either benzene or tetrahydrofuran (THF). An alkynylsamarium is involved as an intermediate.

2,3-Wittig rearrangement by partial reduction of diallyl acetals with SmI2 in acetonitrile

Abstract Diallyl acetals undergo reductive cleavage of an allyloxy group by SmI2 to generate α-allyloxy carbanions, which are transformed into homoallyl alcohols by 2,3-Wittig rearrangement.

Labeling study of avidin by modular method for affinity labeling (MoAL)

We studied the specific labeling of avidin with biotinylated modular ligand catalysts via MoAL, which we recently established. The labeling yield was found to depend on the linker length connecting the catalytic site to biotin in the modular ligand catalyst 1, and the maximum yield was obtained with 1d possessing octamethylene linker. The labeling reaction reached a maximum rate with only 4 equiv of the ligand catalyst. Presumably, all the subunits of avidin with homotetrameric structure formed a stable complex with 4 equiv of the catalyst because of the extremely high affinity. The ligand catalyst bound to avidin first catalyzed N-triazinylation of the ε-amino group of Lys111, and the resulting regenerated catalyst then catalyzed the reaction of Asp108 and CDMT.