Several methodologies for the immobilization of multicomponent asymmetric catalysts (MACs), which consist of two molecules of 1,1'-bi(2-naphthol)(BINOL) and two metals, have been developed. In the first place, Al-Li-bis(binaphthoxide)(ALB) and/or Ga-Na-bis(binaphthoxide)(GaSB) catalysts were introduced to the dendrimers and soluble polymers containing dendron units. Since these dendritic molecules require multi-step synthesis, efficient syntheses of the spherical particles that function like dendrimer-supported catalysts were realized by use of a micelle-derived polymer (MDP) and a monolayer-protected metal cluster (MPC). Secondly, a novel approach based on the use of “catalyst analogue” is found to be effective to position the ligands suitably on the polymer backbone. Thirdly, utilizing metal-bridged polymers, a simple and efficient method for immobilization without the need for a polymer support has also been realized. Heterogeneous ALB, GaSB and μ-oxodititanium complexes thus obtained have been used as catalysts for the asymmetric Michael addition and the asymmetric carbonyl-ene reactions, respectively. The catalysts displayed high activity, affording the corresponding products with high enantiomeric excesses. These catalysts could be recovered and reused.
It was found that low-valent niobium species, which is generated from niobium(V) chloride and lithium aluminum hydride, in situ, is an efficient catalyst for activation of carbon-fluorine bonds. The low-valent niobium species catalyzed 1) hydrodefluorination of fluorobenzenes and α,α,α-trifluorotoluenes, and 2) intramolecular C-C coupling reactions of o-aryl-, o-alkenyl-, and o-alkylamino-α,α,α-trifluorotoluenes. In the latter reactions, fluorenes, indenes, and N-fused indoles were synthesized catalytically in good yields. Nb(0) is supposed to be an active species. Deuterium labeling experiments suggest that niobium fluorocarbenoid intermediates are generated from α,α,α-trifluorotoluenes in the latter C-C coupling reactions.
We found that benzylic carbonates or acetates undergo nucleophilic substitution in the presence of a palladium complex. The palladium catalyst, which is prepared in situ from [Pd(η3-C3H5)(cod)]BF4 and bidentate bisphosphine DPPF, is effective for the reaction of benzyl carbonate with malonate carbanion, giving the desired benzylmalonate in high yield. Choice of the ligand is crucial for the palladium catalysis. Amines, phenols, and sulfinates work as nucleophiles for the palladium-catalyzed benzylic substitution. The activation of the benzylic carbon-oxygen bond with the palladium complex is applied to the cross-coupling of benzyl esters with organometallic compounds or the [4+2] cycloaddition of o-(silylmethyl)benzyl carbonates with alkenes. The latter reaction is equivalent to the Diels-Alder reaction of ortho-quinodimethanes with dienophiles.
Ortho selective direct arylation reactions have been developed using coordination of functional groups to metal complexes. The reaction of 2-arylpyridines with arylstannanes in the presence of rhodium complexes afforded the desired ortho arylated products efficiently. The use of aryl halides also afforded the ortho arylated products by use of ruthenium catalyst. The ruthenium-catalyzed arylation was successfully expanded to 2-alkenylpyridines affording (Z)-β-arylated products selectively. Allylic acetates can be also used in the ruthenium-catalyzed direct coupling reaction of 2-arylpyridines giving the ortho allylated products. On the other hand, the reaction of 2-aryloxazolines with certain allylic acetates gave homo coupling products at their ortho positions.
Indium-mediated reactions have gained increasing popularity over the past decade as environmentally benign tools in organic synthesis. Since the first ionization potential of indium is 5.8 eV, that is as low as those of lithium and sodium, it would be easy for indium(0) to promote SET (single electron transfer) processes. In addition, indium(0) is comparatively stable in air. Indium(III) also attracts considerable attention as water-tolerant and low-toxicity Lewis acid for the activation of C=O and C=N bonds. Herein we describe the development of indium-promoted diastereoselective allylation, radical cyclization, tandem carboindation and coupling reaction, tandem nucleophilic addition and cyclization, and tandem intramolecular nucleophilic attack/intermolecular cycloaddition/dehydration reaction.
Saxitoxin, a paralytic shellfish poison, is potent neurotoxin characterized by highly functionalized architecture including bis-guanidinium and oxygenated pyrrolidine. Recent total syntheses of saxitoxin and its analogue by Du Bois and Nagasawa groups are discussed on this mini review.