Carbenoid, a complex of metal and carbene, undergoes various reactions such as C-H insertion, cyclopropanation, and ylid formation reactions with a range of substrates. Stereo- and chemoselectivity of these reactions is well known to depend upon the nature of the central metal ion and its bystander ligand. Thus, we synthesized new type of optically active metal complexes : bipyridine-copper (I) complex, (salen) cobalt (III) complex, and zinc-1, 1' -bi-2, 2' -naphthol-3, 3' -dicarboxamide complex and used them as catalysts for carbenoid-mediated asymmetric reactions. With these chiral metal complexes, we could achieve i) the first highly enantiospecific ring expansion reaction of oxetane to tetrahydrofurans, ii) highly enantio- and trans-selective cyclopropanation, iii) highly enantioselective Simmons-Smith reaction, and iv) highly stereoselective catalytic [2, 3] Wittig rearrangement. This study greatly expanded the scope of asymmetric carbenoid reactions.
The development of methodologies for the construction of the odd-membered carbocycles such as five- and seven-membered ring systems has become a subject of great interest for synthetic chemists since the ring systems are found in a wide variety of natural products and theoretically interesting molecules. This review describes Brook rearrangement-mediated [3+2] and [3+4] annulation methodologies which permit highly efficient construction of five- and seven-membered carbocycles, respectively.
New method for derivatization of squaric acid was developed by means of Lewis acid-catalyzed reaction of the acid family with unsaturated organosilanes to give 4-substituted 4-hydroxy (or, 4- ethoxy) -2-cyclobutenones. Thermal electrocyclic ring opening of 4-allylated and 4-acylmethylated products was followed by intramolecular [2 + 2] cycloaddition and cyclization of minor stereoisomer of enol ketene to give bicyclo [3.2.0] heptenones and tetronates, respectively. Further, new synthetic potential as a C4-synthon was found in ring transformation of 4-hydroxycyclobutenones involving radical- and cation-mediated ring opening and reclosure processes, which afforded highly substituted 2- (5H) furanones and 4-cyclopentene-1, 3-diones. These reactions included interesting mechanistic features such as 5-endo cyclization of acyl radical, ionic rearrangement of hypoiodite and 1, 2-silylmigration of alkynylsilane. In particular, ab initio calculation for 5-endo cyclization of 5-oxa-2, 4-pentadienoyl radical suggested unusual non-radical cyclization mechanism. The synthetic utility of the above ring transformation strategies was demonstrated in natural product synthesis of (E) -basidalin and (Z) -multicolanate and construction of a triquinane skeleton.
Allenylmethylsilanes have not received so much attention from a synthetic point of view although we can expect various allylsilane and allene chemistry with these molecules. We were, therefore, interested in probing whether we can utilize allenylmethylsilanes as a versatile synthetic reagent. This article deals with (1) preparation of allenylmethylsilanes, (2) their Lewis acid catalyzed reactions with aldehydes or acetals leading to either racemic or chiral alkyl (1, 3-butadien-2-yl) methanols, (3) monoepoxidation of alkyl (1, 3-butadien-2-yl) methanols, generating a new type of epoxy alcohol chiral building blocks, (4) reactions of allenylmethylsilanes with iodine leading to 3-iodo-3-iodomethylallyl-silanes and preparation of 2-iodo-1, 3-butadienes, and (5) synthesis of natural products based on the above-mentioned reactions.
The remarkably high enantioselectivity (k, La, obsd/kDa, obsd = 1000) was attained for the hydrolysis of amino acid esters (N-dodecanoyl-D (L) -phenylalanine p-nitrophenyl ester; C12-D (L) -Phe-PNP) catalyzed by the active tripeptide (N- (benzyloxycarbonyl) -L-phenylalanyl-L-histidyl-L-leucine; Z-Phe-His-Leu) in the coaggregate systems composed of 41 mol% hexadecyltrimethylammonium bromide (CTAB) and 59 mol% ditetradecyldimethylammonium bromide (2 C14Br) at the specific ionic strength (μ =0.02). With respect to the temperature dependence of hydrolysis in the coaggregate systems composed of native lipid (L-α-dipalmitoylphosphatidylcholine; DPPC) and nonionic surfactant (α- [4- (1, 1, 3, 3- tetramethylbutyl) phenyl] -ω-hydroxydecakis (oxyethylene); Triton X-100), the enantioselectivity was maximized at the phase transition temperature (Te) and the hydrophobic microenvironment of coaggregates could be evaluated on the basis of isokinetic temperature (β). On the other hand, in the stereoselective hydrolysis of dipeptide esters as mediated by cyclodextrins (CyD), a high diastereoselectivity (kDL2/kLL2 =46) and preferential binding property (KDLb/KLLb= 2.4) were observed for the hydrolysis of N- (benzyloxycarbonyl) -D (L) -phenylalanyl-L-phenylalanine p-nitrophenyl ester (Z-D (L) -Phe-L-Phe-PNP) by γ-CyD. Furthermore, the computer modeling (MOPAC calculation) study suggests that a favorable molecular recognition between the substrate and catalyst through the effective hydrophobic interactions and hydrogen bonds should be very important for the enhancement of stereoselectivity.
Carbohydrates are important sources of chirality in organic synthesis. We became aware of possible stereocontrol elements, in which the intrinsic molecular architecture of a carbohydrate serves as a template for chirality transcription. Oxidation of diacetone-D-glucose affords 1, 2 : 5, 6-di-O-isopropylidene-α-D-ribo-hexos-3-ulose 1. Each of α- and β-substituents introduced onto the C-3 carbonyl group of 1 must sterically interact with the bulky α-oriented 1, 2-isopropylidene group and the β-oriented substituent at C-4, respectively. These steric interactions may dictate the conformation of the substituents, thereby controlling stereochemistry of reactions on the chiral template 1. Highly enantioselective synthetic method of chiral monodeuterated glycerol, chiral deuterated glycines, chiral amino acids, (2R, 3S) -3-alkylmalic acid, as well as mevalonolactone based on the chiral template 1 and its application to biochemical studies are described.