Kazuaki Ishihara

Quaternary Ammonium (Hypo)iodite Catalysis for Enantioselective Oxidative Cycloetherification

Eye for an I Oxidative catalysis is largely the domain of transition metals, whether iron in an enzyme, or rarer palladium in a synthetic system. These metals can efficiently shuttle between oxidation states, easing the transfer of hydrogen and oxygen atoms between hydrocarbons and oxidants. Uyanik et al. (p. 1376; see the Perspective by French) now show that iodine can take the place of the metal to catalytically activate peroxide during the formation of benzofuran derivatives. Pairing iodide anions with chiral ammonium cations allowed the generation of stereoselectivity at levels similar to those seen with metal complexes bearing chiral ligands. Iodine can effectively replace a transition metal as an electron-transfer catalyst for an organic reaction. It is desirable to minimize the use of rare or toxic metals for oxidative reactions in the synthesis of pharmaceutical products. Hypervalent iodine compounds are environmentally benign alternatives, but their catalytic use, particularly for asymmetric transformations, has been quite limited. We report here an enantioselective oxidative cycloetherification of ketophenols to 2-acyl-2,3-dihydrobenzofuran derivatives, catalyzed by in situ–generated chiral quaternary ammonium (hypo)iodite salts, with hydrogen peroxide as an environmentally benign oxidant. The optically active 2-acyl 2,3-dihydrobenzofuran skeleton is a key structure in several biologically active compounds.

Enantioselective halocyclization of polyprenoids induced by nucleophilic phosphoramidites

Polycyclic bio-active natural products that contain halogen atoms have been isolated from a number of different marine organisms. The biosynthesis of these natural products appears to be initiated by an electrophilic halogenation reaction at a carbon–carbon double bond via a mechanism that is similar to a proton-induced olefin polycyclization. Enzymes such as haloperoxidases generate an electrophilic halonium ion (or its equivalent), which reacts with the terminal carbon–carbon double bond of the polyprenoid, enantioselectively inducing a cyclization reaction that produces a halogenated polycyclic terpenoid. Use of an enantioselective halocyclization reaction is one possible way to chemically synthesize these halogenated cyclic terpenoids; although several brominated cyclic terpenoids have been synthesized via a diastereoselective halocyclization reaction that uses stoichiometric quantities of a brominating reagent, the enantioselective halocyclization of isoprenoids induced by a chiral promoter has not yet been reported. Here we report the enantioselective halocyclization of simple polyprenoids using a nucleophilic promoter. Achiral nucleophilic phosphorus compounds are able to promote the diastereoselective halocyclization reaction to give a halogenated cyclic product in excellent yields. Moreover, chiral phosphoramidites promote the enantioselective halocyclization of simple polyprenoids with N-iodosuccinimide to give iodinated cyclic products in up to 99% enantiomeric excess and diastereomeric excess. To the best of our knowledge, this is the first successful example of the enantioselective halopolycyclization of polyprenoids.

In Situ Generated (Hypo)Iodite Catalysts for the Direct α-Oxyacylation of Carbonyl Compounds with Carboxylic Acids†

a-Acyloxycarbonyl compounds, which are significant building blocks in synthetic organic chemistry, can traditionally be prepared by the substitution reaction of a-halocarbonyl compounds with alkaline carboxylates or the direct oxidative coupling of carbonyl compounds with toxic heavy metal oxidants (i.e. Pb(OAc)4, Tl(OAc)3, Mn(OAc)3, etc.). [2] Recently, the chiral amine catalyzed enantioselective aoxybenzoylation of aldehydes with benzoyl peroxide has also been reported. However, the substrate scope is still limited. Although hypervalent iodine compounds are environmentally benign alternatives to rare or toxic heavy metal oxidants, their use in catalytic amounts is still limited. In 2005, the groups of Ochiai and Kita independently reported the first iodosoarene (ArIL2)-catalyzed oxidative coupling reactions using meta-chloroperbenzoic acid (mCPBA) as a co-oxidant. In particular, Ochiai et al. developed the a-oxyacetylation of ketones catalyzed by the in situ generated iodine(III) in the presence of an excess amount of BF3·Et2O in wet acetic acid [Eq. (1)]. [5a] In 2007,

2-Iodoxybenzenesulfonic Acid as an Extremely Active Catalyst for the Selective Oxidation of Alcohols to Aldehydes, Ketones, Carboxylic Acids, and Enones with Oxone

Electron-donating group-substituted 2-iodoxybenzoic acids (IBXs) such as 5-Me-IBX (1g), 5-MeO-IBX (1h), and 4,5-Me(2)-IBX (1i) were superior to IBX 1a as catalysts for the oxidation of alcohols with Oxone (a trademark of DuPont) under nonaqueous conditions, although Oxone was almost insoluble in most organic solvents. The catalytic oxidation proceeded more rapidly and cleanly in nitromethane. Furthermore, 2-iodoxybenzenesulfonic acid (IBS, 6a) was much more active than modified IBXs. Thus, we established a highly efficient and selective method for the oxidation of primary and secondary alcohols to carbonyl compounds such as aldehydes, carboxylic acids, and ketones with Oxone in nonaqueous nitromethane, acetonitrile, or ethyl acetate in the presence of 0.05-5 mol % of 6a, which was generated in situ from 2-iodobenzenesulfonic acid (7a) or its sodium salt. Cycloalkanones could be further oxidized to alpha,beta-cycloalkenones or lactones by controlling the amounts of Oxone under the same conditions as above. When Oxone was used under nonaqueous conditions, Oxone wastes could be removed by simple filtration. Based on theoretical calculations, we considered that the relatively ionic character of the intramolecular hypervalent iodine-OSO(2) bond of IBS might lower the twisting barrier of the alkoxyperiodinane intermediate 16.

Catalysis with In Situ‐Generated (Hypo)iodite Ions for Oxidative Coupling Reactions

This Concept highlights the discovery and development of oxidative coupling reactions catalyzed by the hypoiodite (IO−) or iodite (OIO−) ion, which are generated in situ from iodide (I−) ion with hydrogen peroxide or tert‐butyl hydroperoxide as an environmentally benign oxidant. The most important features of these catalytic systems are 1) metal‐free oxidation, 2) milder reaction conditions, 3) high chemoselectivity (they tolerate a wide range of various functional groups), 4) operational simplicity, and 5) water or tert‐butyl alcohol as the only byproduct derived from the co‐oxidant used.

Highly enantioselective catalytic Diels-Alder addition promoted by a chiral bis(oxazoline)-magnesium complex

Abstract The new chiral bis(oxazoline) ligand 8 has been synthesized from (S)-phenylglycine and has been shown to form effective catalysts for enantioselective Diels-Alder addition in combination with ferric iodide, magnesium iodide or magnesium tetraphenylborate. Catalytic activation of the dienophile, 3-acryloyl-1,3-oxazolidine-2-one ( 4 ), in the magnesiwn system is proposed to involve tetrahedrally coordinated magnesium in a dipositive complex ( 10 ).

Direct ester condensation from a 1:1 mixture of carboxylic acids and alcohols catalyzed by hafnium(IV) or zirconium(IV) salts

To promote atom efficiency in synthesis and to avoid the generation of environmental waste, the use of stoichiometric amounts of condensing reagents or excess substrates should be avoided. In esterification, excess amounts of either carboxylic acids or alcohols are normally needed. We found that the direct condensation of equimolar amounts of carboxylic acids and alcohols could be achieved using hafnium(IV) or zirconium(IV) salts. These metal salts are highly effective as catalysts for the selective esterification of primary alcohols with carboxylic acids in the presence of secondary alcohols or aromatic alcohols. The present methods can be applied to direct polyesterification and may be suitable for large-scale operations.

ARYLBORON COMPOUNDS AS ACID CATALYSTS IN ORGANIC SYNTHETIC TRANSFORMATIONS

Arylboron compounds, ArnB(OH)3–n (n = 1–3), bearing electron-withdrawing aromatic groups such as triarylboranes, diarylborinic acids, and arylboronic acids represent a new class of air-stable and water-tolerant Lewis acid or Bronsted acid catalysts in organic synthesis. In particular, while tris(pentafluorophenyl)borane has primarily been used as a co-catalyst in metallocene-mediated olefin polymerization, its potential as a Lewis acid catalyst for organic transformation is now much more extensive. Diarylborinic acids and arylboronic acids have shown themselves to be powerful tools in the design of chiral boron catalysts. This article provides a comprehensive summary of the organic transformations catalyzed by arylboron compounds as acids.

High-turnover hypoiodite catalysis for asymmetric synthesis of tocopherols

Iodine blooms as an oxidation catalyst Most catalysts for organic oxidation chemistry—whether biochemical or artificial—contain a transition metal like iron or palladium. Uyanik et al. now show that iodine can take the place of a metal in catalyzing efficient oxidative ring closures to make chromans—hexagonal rings incorporating oxygen that are perhaps best known as a constituent of the vitamin E structure (see the Perspective by Nachtsheim). The iodine is added as a salt with a chiral cation, which directs the reaction to form just one of two possible mirror-image variants of the product. Key to the success of the system was the addition of a base, which maintained the viability of an unstable, partially oxidized iodine intermediate critical to the reaction cycle. The results bode well for more general use of iodine salts as asymmetric oxidation-reduction catalysts. Science, this issue p. 291; see also p. 270 An iodide salt with a chiral counterion proves an efficient catalyst for preparation of compounds analogous to vitamin E. [Also see Perspective by Nachtsheim] The diverse biological activities of tocopherols and their analogs have inspired considerable interest in the development of routes for their efficient asymmetric synthesis. Here, we report that chiral ammonium hypoiodite salts catalyze highly chemo- and enantioselective oxidative cyclization of γ-(2-hydroxyphenyl)ketones to 2-acyl chromans bearing a quaternary stereocenter, which serve as productive synthetic intermediates for tocopherols. Raman spectroscopic analysis of a solution of tetrabutylammonium iodide and tert-butyl hydroperoxide revealed the in situ generation of the hypoiodite salt as an unstable catalytic active species and triiodide salt as a stable inert species. A high-performance catalytic oxidation system (turnover number of ~200) has been achieved through reversible equilibration between hypoiodite and triiodide in the presence of potassium carbonate base. We anticipate that these findings will open further prospects for the development of high-turnover redox organocatalysis.

Zinc(II)-Catalyzed Addition of Grignard Reagents to Ketones

The addition of organometallic reagents to carbonyl compounds has become a versatile method for synthesizing tertiary and secondary alcohols via carbon-carbon bond formation. However, due to the lack of good nucleophilicity or the presence of strong basicity of organometallic reagents, the efficient synthesis of tertiary alcohols from ketones has been particularly difficult and, thus, limited. We recently developed highly efficient catalytic alkylation and arylation reactions to ketones with Grignard reagents (RMgX: R = alkyl, aryl; X = Cl, Br, I) using ZnCl(2), Me(3)SiCH(2)MgCl, and LiCl, which effectively minimize problematic side reactions. In principle, RMgBr and RMgI are less reactive than RMgCl for the addition to carbonyl compounds. Therefore, this novel method with homogeneous catalytic ZnCl(2) x Me(3)SiCH(2)MgCl x LiCl is quite attractive, since RMgBr and RMgI, which are easily prepared and/or commercially available, like RMgCl, can be applied successfully. As well as ketones and aldehydes, aldimines were effectively applied to this catalysis, and the corresponding secondary amines were obtained in high yield. With regard to mechanistic details concerning beta-silyl effect and salt effect, in situ-prepared [R(Me(3)SiCH(2))(2)Zn](-)[Li](+)[MgX(2)](m)[LiCl](n) (X = Cl/Br/I) is speculated to be a key catalytic reagent to promote the reaction effectively. The simplicity of this reliable ZnCl(2) x Me(3)SiCH(2)MgCl x LiCl system in the addition of Grignard reagents to carbonyl compounds might be attractive for industrial as well as academic applications.