A one-pot synthetic method was developed for multifunctional dihydrooxazole and oxazole derivatives. New reaction sequences were developed involving the formation of isocyanide dichloride, an aldol-type reaction with aldehydes, and a nucleophilic addition–elimination reaction, which efficiently afforded the dihydrooxazole and oxazole scaffolds.

An enantioselective formal total synthesis of (+)-manzacidin C is described. A key feature of the synthesis is the construction of two chiral centers via the asymmetric 1,3-dipolar cycloaddition of an azomethine imine to methallyl alcohol by the use of (S,S)-DIPT as a chiral auxiliary.

The reaction of (Z)-hydroximoyl chlorides with isocyanides promoted by phosphinic acid in the presence of triethylamine proceeds smoothly to afford α-(hydroxyimino)amides in good to high yields. Phosphinic acid plays an important role in effectively promoting the reaction. A wide range of (Z)-hydroximoyl chlorides and isocyanides were found to be suitable for this reaction.

We developed a [4+1] cycloaddition reaction of isocyanides with 2-mercaptobenzaldehydes and/or their disulfide derivatives, promoted by LiI·2H2O, to afford benzothiophene derivatives in moderate to good yields. Isocyanides, 2-mercaptobenzaldehydes and disulfide derivatives of various types were used successfully in the reaction.

Asymmetric 1,2-addition of dialkylzinc reagents to α,β-unsaturated N-tosylaldimines was catalyzed by copper salt in the presence of chiral imidazolium salts having a pyridine ring, which were derived from amino acid, to afford the corresponding chiral allylic amines with up to 91% ee in reasonably high yields. The chiral N-heterocyclic carbene (NHC) ligand played an important role in controlling chemoselectivity.

We have developed a one-pot O-sulfinative Passerini/oxidation reaction, in which a combination of an aldehyde, an isocyanide, and a sulfinic acid react, followed by the addition of mCPBA as an oxidant to give the corresponding α-(sulfonyloxy)amides in high yields. This reaction is the first reported demonstration of an isocyanide-based multicomponent reaction using a sulfinic acid in place of a carboxylic acid. A wide range of aldehydes and isocyanides are applicable to this reaction.

The stereoselective transformation of α-alkoxyacetoaldehydes to the corresponding (Z)-vinyl triflates was achieved by treatment with phenyl triflimide and DBU. The stereochemistry was explained by the “syn-effect,” which was attributed primarily to an σ → π* interaction. The β-alkoxy vinyl triflates obtained were applied to the stereoselective synthesis of structurally diverse (Z)-allylic alcohols via transition metal-catalyzed cross-coupling reaction and [1,2]-Wittig rearrangement.

Highly efficient formation of 3-benzazepine derivatives has been achieved, based on the ring expansion reaction of C,N-cyclic-N′-acyl azomethine imines with sulfonium ylide generated in situ from the corresponding sulfonium salt. The reactions proceeded smoothly to afford the tricyclic 3-benzazepine derivatives in good to high yields. A wide range of C,N-cyclic N′-acyl azomethine imines were applicable to this reaction.

Desymmetrization of various meso-methylenecyclopropanes was accomplished by a palladium-catalyzed asymmetric ring-opening bis(alkoxycarbonylation) reaction employing a chiral bioxazoline ligand. The reaction proceeded smoothly in the presence of copper(I) triflate under carbon monoxide and oxygen at ambient pressure to give the corresponding optically active α-methyleneglutarates with up to 60% ee. Desymmetrization of protected meso-(3-methylenecyclopropane-1,2-diyl)dimethanols was also carried out to give enantioenriched highly oxygen-functionalized α-methyleneglutarates.(S,S)-4,4′-Bis(1-naphthalenylmethyl)-4,4′,5,5′-tetrahydro-2,2′-bioxazoleC28H24N2O2Ee = 100%[α]D25 = −5 (c 0.9, CHCl3)Source of chirality: (S)-2-amino-3-(1-naphthalenyl)-1-propanolAbsolute configuration: (S,S)(R,R)-4,4′-Bis(2-naphthalenylmethyl)-4,4′,5,5′-tetrahydro-2,2′-bioxazoleC28H24N2O2Ee = 100%[α]D25 = −26 (c 0.3, CHCl3)Source of chirality: (R)-2-amino-3-(2-naphthaleny)-1-propanolAbsolute configuration: (R,R)(1R,2S)-Methyl 2-(3-methoxy-3-oxo-1-propen-2-yl)cyclohexanecarboxylateC12H18O4Ee = 60%[α]D25 = −49 (c 0.6, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (1R,2S)(1R,2S)-Methyl 2-(3-methoxy-3-oxo-1-propen-2-yl)cyclooctanecarboxylateC14H22O4Ee = 45%[α]D25 = −11 (c 0.1, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (1R,2S)(2S,3S)-Dimethyl 2,3-bis((benzyloxy)methyl)-4-methylenepentanedioateC24H28O6Ee = 28%[α]D25 = +6 (c 1.3, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (2S,3S)(3S,4S)-Dimethyl 2-methylene-3,4-bis((trityloxy)methyl)pentanedioateC48H44O6Ee = 42%[α]D25 = +5 (c 0.5, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (3S,4S)(3S,4S)-Dimethyl 2-methylene-3,4-bis((triphenylsilyloxy)methyl)pentanedioateC46H44O6Si2Ee = 48%[α]D25 = +6 (c 1.5, CHCl3)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (3S,4S)(2S,3S)-Dimethyl 2,3-bis((tert-butyldiphenylsilyloxy)methyl)-4-methylenepentanedioateC42H52O6Si2Ee = 51%[α]D25 = +3 (c 1.9, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (2S,3S)(1S,4R)-2-((1S,2R)-2-((((1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carbonyl)oxy)methyl)cyclohexyl)allyl 4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylateC30H42O8Ee = 100%[α]D25 = −11 (c 0.1, EtOH)Source of chirality: asymmetric ring-opening bis(alkoxycarbonylation) reactionAbsolute configuration: (1S,4R),(1S,2R),(1S,4R)

The oxidative coupling reaction of aldehydes with N,N′-disubstituted carbodiimides catalyzed by N-heterocyclic carbenes under aerobic conditions has been achieved. This reaction gives the corresponding N-acylurea derivatives in good to high yields. Various kinds of aldehydes including aliphatic ones and carbodiimides are applicable to this reaction.

An asymmetric Strecker-type reaction of nitrones using acetone cyanohydrin as a source of HCN has been realized. A magnesium–tartramide complex, generated from (R,R)-2,3-dihydroxy-1,4-di(pyrrolidin-1-yl)-butane-1,4-dione and MeMgBr, promoted transcyanation from the bromomagnesium salt of the cyanohydrin, in the presence of a catalytic amount of DBU, to afford the corresponding optically active (S)-α-amino nitrile derivatives. The reaction was applicable to various nitrones giving high-to-excellent enantioselectivities.

A multicomponent reaction of isocyanides and C,N-cyclic N′-acyl azomethine imines in the presence of TMSCl and NaN3 leads to tetrazole derivatives. These reactions proceeded cleanly to afford the corresponding 1,5-disubstituted tetrazoles containing a tetrahydroisoquinoline skeleton in high to excellent yields.

The sequential 1,4-elimination reaction of (E)-4-alkoxy-2-butenyl benzoates and [1,2]-Wittig rearrangement gave (2Z,4E)-2,4-pentadien-1-ols stereoselectively. Z-Selective formation of intermediary vinyl ethers, whose stereochemistry was well elucidated by the “syn-effect”, was achieved by treatment of the 2-butenyl benzoates with KOH in the presence of Pd catalyst. The subsequent [1,2]-Wittg rearrangement by use of n-BuLi proceeded with retention of the stereochemistry of the intermediary vinyl ethers.

A multicomponent reaction of isocyanides and C,N-cyclic N′-acyl azomethine imines in the presence of TMSCl and NaN3 leads to tetrazole derivatives. These reactions proceeded cleanly to afford the corresponding 1,5-disubstituted tetrazoles containing a tetrahydroisoquinoline skeleton in high to excellent yields.

The reaction of (Z)-hydroximoyl chlorides with isocyanides promoted by phosphinic acid in the presence of triethylamine proceeds smoothly to afford α-(hydroxyimino)amides in good to high yields. Phosphinic acid plays an important role in effectively promoting the reaction. A wide range of (Z)-hydroximoyl chlorides and isocyanides were found to be suitable for this reaction.