Enantiospecific Sn(II)- and Sn(IV)-catalyzed cycloadditions of aldehydes and donor-acceptor cyclopropanes

A cycloaddition strategy for the synthesis of highly enantioenriched 2,5-cis-disubstituted tetrahydrofurans has been developed. In the presence of catalytic Sn(OTf)2 or SnCl4, a range of aldehydes will undergo formal [3 + 2] cycloadditions with a scalemic donor-acceptor cyclopropane to form optically active heterocycles. Mechanistic studies support an unusual SN2 attack by the aldehyde on the activated cyclopropane. Through this mechanism, stereochemical information contained in the cyclopropane is effectively transferred to the tetrahydrofuran products.     

Functionalized tetrahydrofurans from alkenols and olefins/alkynes via aerobic oxidation-radical addition cascades

Aerobic oxidation of alkyl- and phenyl-substituted 4-pentenols (bishomoallyl alcohols), catalyzed by cobalt(II) complexes in solutions of γ-terpinene or cyclohexa-1,4-diene, stereoselectively gave tetrahydrofurylmethyl radicals. Cyclized radicals were trapped with monosubstituted olefins (e.g., acrylonitrile, methyl acrylate), (E)- and (Z)-1,2-diacceptor-substituted olefins (e.g., dimethyl fumarate, fumarodinitrile, N-phenyl maleic imide), and ester-substituted alkynes (e.g., ethyl propynoate). Oxidation-addition cascades thus furnished side-chain-substituted (CN, CO(2)R, COR, or SO(2)R) di- and trisubstituted tetrahydrofurans in stereoselective reactions (2,3-trans, 2,4-cis, and 2,5-trans). A diastereomerically pure bistetrahydrofuran was prepared in a cascade consisting of two aerobic oxidations, one alkyne addition, and one final H-atom transfer.     

Use of hindered silyl ethers as protecting groups for the non-aldol aldol process

[reaction: see text] Bulky epoxy bis-silyl ethers, e.g., 15, derived from 5-trialkylsilyloxy-2-alken-1-ols by epoxidation and silylation were treated with TMSOTf to afford non-aldol aldol rearrangement products, the 3,5-bis(silyloxy)alkanals, e.g., 16, with little to none of the corresponding tetrahydrofurans.     

Unexpected C-H activation of Ru(II)-dithiomaltol complexes upon oxidation

Thione-substituted derivatives of maltol are of interest in several applications of metal-based drugs. In order to investigate the effect of the oxygenation on such thione chelates, Ru complexes of 3-hydroxy-2-methyl-4-thiopyrone (thiomaltol or Htma) and 3-hydroxy-2-methyl-4H-thiopyran-4-thione (dithiomaltol or Httma), [Ru(bpy)2(tma)](+), 1, and [Ru(bpy) 2(ttma)] (+), 2, were synthesized as diamagnetic PF6(-) salts. Peroxidation of 2 unexpectedly generated products of C-H activation at its pendant methyl group; an air-stable aldehyde [Ru(bpy)2(ttma-aldehyde)](+), 4, was the major product. In addition, an intermediate oxidation product [Ru(bpy) 2(ttma-alcohol)](PF6), 3, was characterized. Both 3 and 4 are also formed by reaction of 2 with outersphere oxidants (e.g., Na2IrCl6) and by bulk electrolysis under anaerobic conditions. Similar oxidations of the analogous [Ru(bpy)2(ettma)](+), 2' , complex (3-hydroxy-2-ethyl-4H-thiopyran-4-thione; ethyl dithiomaltol or Hettma) formed the corresponding ketone, [Ru(bpy)2(ettma-ketone)](PF6), 4', by oxidation at the same position adjacent to the conjugated ring. The structures of the aldehyde 4 and starting materials 1 and 2 have been confirmed by X-ray crystallography, and all complexes have been characterized by UV-vis, (1)H NMR, and IR spectroscopies. Initial mechanistic investigations are discussed.     

Diastereoselective conjugate additions to pi-allylmolybdenum complexes: a stereocontrolled route to 3,4,5-trisubstituted gamma-butyrolactones

[reaction: see text] pi-Allylmolybdenum complex 6b is obtained as a single isomer by Knoevenagel condensation of aldehyde 1 with Meldrum's acid. Conjugate additions of Grignard reagents to Meldrum's acid alkylidene derivative 6b are shown to be completely diastereoselective. Further functional group transformation of the 1,4-adducts, followed by demetalation, leads to trisubstituted tetrahydrofurans and gamma-butyrolactones. Whereas the synthesis of tetrahydrofurans (X = 2H) is not completely stereoselective, the gamma-butyrolactones (X = O) are obtained with good to excellent diastereoselectivities.     

Reactivities of mononuclear non-heme iron intermediates including evidence that iron(III)-hydroperoxo species is a sluggish oxidant

There is an intriguing, current controversy on the involvement of iron(III)-hydroperoxo species as a "second electrophilic oxidant" in oxygenation reactions by heme and non-heme iron enzymes and their model compounds. In the present work, we have performed reactivity studies of the iron-hydroperoxo species in nucleophilic and electrophilic reactions, with in situ-generated mononuclear non-heme iron(III)-hydroperoxo complexes that have been well characterized with various spectroscopic techniques. The intermediates did not show any reactivities in the nucleophilic (e.g., aldehyde deformylation) and electrophilic (e.g., oxidation of sulfide and olefin) reactions. These results demonstrate that non-heme iron(III)-hydroperoxo species are sluggish oxidants and that the oxidizing power of the intermediates cannot compete with that of high-valent iron(IV)-oxo complexes. We have also reported reactivities of mononuclear non-heme iron(III)-peroxo and iron(IV)-oxo complexes in the aldehyde deformylation and the oxidation of sulfides, respectively.     

Dual-activation protocol for tandem cross-aldol condensation: An easy and highly efficient synthesis of α,α′-bis(aryl/alkylmethylidene)ketones

Commercially available lithium hydroxide monohydrate (LiOH·H₂O) was found to be a novel ‘dual activation’ catalyst for tandem cross-aldol condensation between cyclic/acyclic ketones and aromatic/heteroaromatic/styryl/alkyl aldehydes leading to an efficient and easy synthesis of α,α′-bis(aryl/alkylmethylidene)ketones at r.t. in short times. The reaction of aryl, heteroaryl, styryl and alkyl aldehydes with acyclic and five/six-membered cyclic ketones afforded excellent yields after 2 min to 1.25 h. The reaction conditions were compatible with various electron withdrawing and electron donating substituents, e.g. Cl, F, NO₂, OMe and NMe₂. The rate of the cross-aldol condensation was influenced by the nature of the ketone and electronic and steric factors associated with the aldehyde. The reaction took place at a faster rate for acyclic ketone (e.g., acetone) than that for cyclic ketone (e.g., cyclohexanone). In case of cycloalkanones, the rate of the reaction was dependent on the size of the ring of the cycloalkanone. The cross-aldol condensation of cyclopentanone was faster than that of cyclohexanone for a common aldehyde. In case of reactions involving aliphatic aldehyde having α-hydrogen atom no self-aldol condensation of the aldehyde took place.     

Regioselective and stereoselective synthesis of tetrahydrofurans from a functionalized allylic silane and an aldehyde via formal [3+2]-cycloaddition reaction

Allylsilanes are known as useful reagents for the stereoselective formation of ring systems. Previous studies have shown that tetrahydrofurans can be constructed via formal [3+2]-cycloadditions of aldehydes and allylsilanes. A new challenge is to understand the intermediate, after a nucleophile attacks a carbonyl activated by the Lewis acid, in which two silyl-protected alkoxy groups with chemical equivalency could undergo formal cycloaddition reaction to afford a disubstituted and/or a trisubstituted tetrahydrofuran. Preparation of the protected α-hydroxy aldehyde and a functionalized allylic silane is discussed, as well as their formal cycloaddition reaction to form tetrahydrofurans.     

Systematic modulation of a bichromic cyclometalated ruthenium(II) scaffold bearing a redox-active triphenylamine constituent

The syntheses and physicochemical properties of nine bis-tridentate ruthenium(II) complexes containing one cyclometalating ligand furnished with terminal triphenylamine (TPA) substituents are reported. The structure of each complex conforms to a molecular scaffold formulated as [Ru(II)(TPA-2,5-thiophene-pbpy)(Me(3)tctpy)] (pbpy = 6-phenyl-2,2'-bipyridine; Me(3)tctpy = trimethyl-4,4',4'-tricarboxylate-2,2':6',2'-terpyridine), where various electron-donating groups (EDGs) and electron-withdrawing groups (EWGs) are installed about the TPA unit and the anionic ring of the pbpy ligand. It is found that the redox chemistry of the Ru center and the TPA unit can be independently modulated by (i) placing EWGs (e.g., -CF(3)) or EDGs (e.g., -OMe) on the anionic ring of the pbpy ligand (substituted sites denoted as R(2) or R(3)) and/or (ii) installing electron-donating substituents (e.g., -H, -Me, -OMe) para to the amine of the TPA group (i.e., R(1)). The first oxidation potential is localized to the TPA unit when, for example, EDGs are placed at R(1) with EWGs at R(2) (e.g., the TPA(?+)/TPA(0) and Ru(III)/Ru(II) redox couples appear at +0.98 and +1.27 V vs NHE, respectively, when R(1) = -OMe and R(2) = -CF(3)). This situation is reversed when R(3) = EDG and R(1) = -H: TPA-based and metal-centered oxidation waves occur at +1.20 and +1.11 V vs NHE, respectively. The UV-vis spectrum for each complex is broad (e.g., absorption bands are extended from the UV region to beyond 800 nm in all cases) and intense (e.g., ε ～ 10(4) M(-1)·cm(-1)) because of the overlapping intraligand charge-transfer and metal-to-ligand charge-transfer transitions. The information derived from this study offers guiding principles for modulating the physicochemical properties of bichromic cyclometalated ruthenium(II) complexes.     

Total synthesis and proof of relative stereochemistry of (-)-aureonitol

Two trisubstituted epimeric tetrahydrofurans, 1 and 2, have been synthesized in order to confirm the relative stereochemistry in the natural product aureonitol. The key step in the synthesis of 1 and 2 involved a stereoselective intramolecular allylation of an allylsilane with an aldehyde, which introduced the stereotriad in the five-membered ring. The major tetrahydrofuran diastereoisomer 18 from this cyclization reaction was subsequently elaborated to tetrahydrofuran 1. Its 3-epimer (2) was then prepared from 1 via an oxidation-reduction sequence. Compound 1 exhibits identical (1)H NMR data to those reported for aureonitol, which was isolated from Helichrysum aureonitons by Bohlmann in 1979, whereas the (1)H NMR data for 2 are markedly different. The (1)H NMR data (in CDCl3, CD3OD, and C6D6) and (13)C NMR data (in CDCl3) for 1 are also identical with those reported for a natural product isolated from various Chaetomium sp. by Abraham, Seto, and Teuscher. These findings support Abraham's conclusion that the structure of aureonitol should be revised from 2 to 1. The enantioselective synthesis of 1 has also confirmed that (-)-aureonitol isolated by Abraham contains the (2S,3R,4S) absolute configuration of stereocenters on the tetrahydrofuran ring.     

Stereoselective synthesis of 3,4-disubstituted tetrahydrofurans and 2,3,4-trisubstituted tetrahydrofurans using an intramolecular allylation strategy employing allylsilanes

A Brønsted acid-mediated intramolecular allylation involving an allylsilane and an aldehyde has been used as the key step in a stereoselective synthesis of 3,4-disubstituted tetrahydrofurans and 2,3,4-trisubstituted tetrahydrofurans.     

Intramolecular hydroalkoxylation of <Emphasis Type="Italic">syn</Emphasis>- and <Emphasis Type="Italic">anti</Emphasis>-1-R-2-arylhex-4-en-1-ols. Efficient stereoselective synthesis of tri- and tetrasubstituted tetrahydrofurans

Reactions of syn- and anti-4-(4-bromophenyl)-2-methylnon-1-en-5-ols and 3-(4-bromophenyl)-5- methyl-1-phenylhex-5-en-2-ols with trifluoromethanesulfonic acid and salicylaldehyde derivatives in the presence of Et₂O · BF₃ (Prins reaction) or with salicylaldehydes in the presence of trimethyl orthoformate and p-toluenesulfonic acid stereoselectively afforded tri- and tetrasubstituted tetrahydrofurans with one or two fused heterocycles and various functional groups (COOEt, Br, MeC=CH₂). The reactivity of the synthesized compounds toward thiophen-2-ylboronic acid in the Suzuki reaction was studied, and hydrolysis and reduction (LiAlH₄) of the ester group therein gave the corresponding carboxylic acids and alcohols. One of the obtained tetrahydrofuran derivatives was converted into amide, aldehyde, and aldehyde oxime. Stereochemical configuration of substituents was retained in all chemical transformations.     

Stereocontrolled construction of tetrahydrofurans and gamma-butyrolactones using organomolybdenum chemistry

[reaction: see text]. Diastereoselective conversion of pi-allylmolybdenum complex aldehyde 1 to organometallic triol 4 and diols 5, 10, and 13 is described. Stereocontrolled demetalation of 4, 5, and 13 was accomplished, leading to hydroxylated tetrahydrofurans and gamma-butyrolactones, as single diastereoisomers.     

Hydrothermal synthesis of ultralong and single-crystalline Cd(OH)2 nanowires using alkali salts as mineralizers

Ultralong and single-crystalline Cd(OH)(2) nanowires were fabricated by a hydrothermal method using alkali salts as mineralizers. The morphology and size of the final products strongly depend on the effects of the alkali salts (e.g., KCl, KNO(3), and K(2)SO(4) or NaCl, NaNO(3), and Na(2)SO(4)). When the salt is absent, only nanoparticles are observed in TEM images of the products. The 1D nanostructure growth method presented herein offers an excellent tool for the design of other advanced materials with anisotropic properties. In addition, the Cd(OH)(2) nanowires might act as a template or precursor that is potentially converted into 1D cadmium oxide through dehydration or into 1D nanostructures of other functional materials (e.g., CdS, CdSe).     

An extremely efficient three-component reaction of aldehydes/ketones, amines, and phosphites (Kabachnik-Fields reaction) for the synthesis of alpha-aminophosphonates catalyzed by magnesium perchlorate

Commercially available magnesium perchlorate is reported as an extremely efficient catalyst for the synthesis of alpha-aminophosphonates. A three-component reaction (3-CR) of an amine, an aldehyde or a ketone, and a di-/trialkyl phosphite (Kabachnik-Fields reaction) took place in one pot under solvent-free conditions to afford the corresponding alpha-aminophosphonates in high yields and short times. The use of solvent retards the rate of the reaction and requires a much longer reaction time than that for neat conditions. The reactions involving an aldehyde, an aromatic amine without any electron-withdrawing substituent, and a phosphite are carried out at rt. The reactions involving cyclic ketones, aromatic amines with an electron-withdrawing substituent, and aryl alkyl ketone (e.g., acetophenone) require longer reaction times at rt or heating. Magnesium perchlorate was found to be superior to other metal perchlorates and metal triflates during the reaction of 4-methoxybenzaldehyde, 2,4-dinitroaniline, and dimethyl phosphite. The catalytic activity of various magnesium compounds was influenced by the counteranion, and magnesium perchlorate was found to be the most effective. The reaction was found to be general with di-/trialkyl phosphites and diaryl phosphite. The Mg(ClO4)2-catalyzed alpha-aminophosphonate synthesis in the present study perhaps represents a true three-component reaction as no intermediate formation of either an imine or alpha-hydroxy phosphonate was observed that indicated the simultaneous involvement of the carbonyl compound, the amine, and the phosphite in the transition state.     

Crystal Structure of 2-thiophene-2-yl-3(thiophene-2-carboxylideneamino)-1, 2-dihydroquinazolin-4(3H)-one and the Synthesis, Spectral and Thermal Studies of its Transition Metal(II) Complexes

The synthesis of manganese(II), cobalt(II), nickel(II), copper(II), zinc(II) and cadmium(II) complexes of a new ligand 2-thiophene-2-yl-3(thiophene-2-carboxylidene-amino)-1,2-dihydroquinazolin-4(3H)-one (TTCADQ) is described. The ligand and metal complexes were characterized by elemental analysis, conductivity measurements, spectral (u.v.–vis., i.r., 1D n.m.r., 2D hetcor and e.p.r.) and thermal studies. The formation of 1,2-dihydroquinazolin-4(3H)-one rather than hydrazone, in the reaction of aromatic aldehyde and o-aminobenzoylhydrazide is proved by single crystal X-ray diffraction and 2D hetcor n.m.r. studies. On the basis of elemental analysis, u.v.–vis.spectroscopy and magnetic moment studies, six coordinate geometry for all the complexes was proposed. The i.r. spectral studies reveal the bidentate behaviour of the ligand.     

Stereoselective synthesis of (2R,3S,4S,5R)-trans-3,4-dihydroxy-5-(4-fluorophenoxymethyl)-2-(1-N-hydroxyureidyl-3-butyn-4-yl)tetrahydrofuran and (2R,3S,4S,5R)-trans-5-ethynyl-2-(4-fluorophenoxymethyl)-3,4-O-isopropylidene tetrahydrofuran from mannose diacetonide

Stereoselective synthesis of pharmaceutically interesting chiral tetrahydrofurans starting from mannose diacetonide is reported. A 1,4-diol system derived from mannose diacetonide, through a Mitsunobu reaction was stereospecifically cyclized to give chiral tetrahydrofurans. Both the C-1 and C-4 centers of d-mannose are successfully exploited to install the requisite side chains.     

Neutron scattering studies of K(3)H(SO(4))(2) and K(3)D(SO(4))(2): The particle-in-a-box model for the quantum phase transition

In the crystal of K(3)H(SO(4))(2) or K(3)D(SO(4))(2), dimers SO(4)???H???SO(4) or SO(4)???D???SO(4) are linked by strong centrosymmetric hydrogen or deuterium bonds whose O???O length is ≈2.50 A?. We address two open questions. (i) Are H or D sites split or not? (ii) Is there any structural counterpart to the phase transition observed for K(3)D(SO(4))(2) at T(c) ≈ 85.5 K, which does not exist for K(3)H(SO(4))(2)? Neutron diffraction by single-crystals at cryogenic or room temperature reveals no structural transition and no resolvable splitting of H or D sites. However, the width of the probability densities suggest unresolved splitting of the wavefunctions suggesting rigid entities H(L1∕2) -H(R1∕2) or D(L1∕2) -D(R1∕2) whose separation lengths are l(H) ≈ 0.16 A? or l(D) ≈ 0.25 A?. The vibrational eigenstates for the center of mass of H(L1∕2) -H(R1∕2) revealed by inelastic neutron scattering are amenable to a square-well and we suppose the same potential holds for D(L1∕2) -D(R1∕2). In order to explain dielectric and calorimetric measurements of mixed crystals K(3)D((1 - ρ))H(ρ)(SO(4))(2) (0 ≤ ρ ≤ 1), we replace the classical notion of order-disorder by the quantum notion of discernible (e.g., D(L1∕2) -D(R1∕2)) or indiscernible (e.g., H(L1∕2) -H(R1∕2)) components depending on the separation length of the split wavefunction. The discernible-indiscernible isostructural transition at finite temperatures is induced by a thermal pure quantum state or at 0 K by ρ.     

Zinc(II) perchlorate as a new and highly efficient catalyst for formation of aldehyde 1,1-diacetate at room temperature and under solvent-free conditions

Zinc(II) perchlorate efficiently catalysed the conversion of aromatic, heteroaromatic, and aliphatic aldehydes to 1,1-diacetates under solvent-free conditions at room temperature. It was compatible with other functional groups (e.g., ether, ester, nitro, and cyano) likely to interfere by complex formation with the catalyst. Other anhydrides such as isobutyric, pivalic, and benzoic anhydrides afforded the corresponding 1,1-dicarboxylates and established the generality. The reaction rate was influenced by the steric and electronic nature of the anhydride. The rate of 1,1-dicarboxylate formation was found to follow the order Ac₂O > (i-PrCO)₂O > (t-BuCO)₂O > (PhCO)₂O and no 1,1-dicarboxylate formation took place with (ClCH₂CO)₂O, and (F₃CO)₂O. During inter- and intra-molecular competition between a ketone and an aldehyde group with Ac₂O, 1,1-diacetate formation took place exclusively with the aldehyde group. An 88:12 selectivity was observed for 1,1-diacetate formation in favour of 1-naphthaldehyde during competition with 2-methoxy-1-naphthaldehyde.     

Ruthenium-catalyzed transformation of 3-benzyl but-1-ynyl ethers into 1,3-dienes and benzaldehyde via transfer hydrogen

TpRuPPh(3)(CH(3)CN)(2)PF(6) catalyzed the transformation of various 3-benzyl but-1-ynyl ethers into dienes and benzaldehyde at a catalyst loading of 5 mol %. This process represents an atypical pattern of transfer hydrogenation. This catalytic reaction can be applied to various derivatives of 2-ethynyl tetrahydrofurans and pyrans to cleave their ether rings and gives diene and tethered aldehyde functionalities, respectively.