Copper diisobutyl-t-butoxyaluminum hydride: A novel reagent for chemoselective reduction of tertiary amides over esters

We demonstrate that copper diisobutyl-t-butoxyaluminum hydride, readily prepared from lithium diisobutyl-t-butoxyaluminum hydride and CuI, effectively and chemoselectively reduces tertiary amides over esters at ambient temperature, affording the corresponding aldehydes in excellent yields.     

Lithium diisobutyl-t-butoxyaluminum hydride, a new and efficient reducing agent for the conversion of esters to aldehydes

Lithium diisobutyl-t-butoxyaluminum hydride (LDBBA), easily prepared by reaction of lithium t-butoxide with DIBALH, readily reacts with common aromatic and aliphatic esters to give the corresponding aldehydes in 74-88% yield at 0 °C. Especially, this reagent proved to be the most effective partial reducing agent for conversion of isopropyl esters to aldehydes, in most cases, with >90% yield under the same reaction temperature.     

Reaction of lithium tris(tert-butylthiolato)hydridoaluminate with selected organic compounds containing representative functional groups

The approximate rates and stoichiometry of the reaction of lithium tri(2-methyl-2-propanethioxy)aluminum hydride (LTBSA) with selected organic compounds containing representative functional groups under the standardized conditions (tetrahydrofuran, 0 °C) were studied in order to define the reducing ability of LTBSA also compared with those of the parent lithium aluminum hydride (LAH) and lithium t-butoxyaluminum hydride (LTBA).     

Facile transformation of esters to nitriles

Various esters were efficiently converted into the corresponding nitriles in good yields by the treatment with sodium diisobutyl-tert-butoxyaluminium hydride (SDBBA-H), followed by treatment with molecular iodine in aq ammonia. The present one-pot method is very efficient and practical for the conversion of various aromatic and aliphatic esters into the corresponding nitriles.     

Chemoselective Carbonyl Reduction Mediated By Low-Valent Titanium

Utilizing the rate difference in alkoxy alkyl radical formation from aldehydes versus ketones with low-valent titanium, aldehydes are preferentially reduced with tributyltin hydride. The difference in reactivity allows aldehydes to be reduced in the presence of ketones without laborious protection-deprotection steps.     

A synthesis of optically active α-quaternary α-amino acids and esters by assembling three components, ketones, (R)-chloromethyl p-tolyl sulfoxide, and sodium azide, via sulfinyloxiranes

Treatment of lithium α-sulfinyl carbanion of chloromethyl p-tolyl sulfoxides with ketones at low temperature afforded adducts in almost quantitative yields, which were exposed to t-BuOK to give sulfinyloxiranes in high yields. The sulfinyloxirane was reacted with benzylamine to give α-amino aldehyde, which was oxidized with iodine in methanol to afford α-amino carboxylic ester in moderate yield. The sulfinyloxiranes were treated with sodium azide to afford α-azido aldehydes in good yields. Oxidation with NaClO₂ followed by catalytic hydrogenation of the azido group of the α-azido aldehydes gave α-quaternary α-amino acids in good overall yields. The oxidation of the azido aldehydes with iodine in methanol in the presence of KOH followed by the catalytic hydrogenation resulted in α-quaternary α-amino acid methyl esters in good yields. When these reactions were carried out starting from unsymmetrical ketones and optically pure (R)-chloromethyl p-tolyl sulfoxide, a new method for a synthesis of optically active α-quaternary α-amino acids and esters in good overall yields was realized.     

A highly diastereoselective approach to tetrahydrofurans via [3+2] cycloadditions of silylmethyl-substituted cyclopropanes with aldehydes and ketones

An efficient and highly diastereoselective synthesis of highly substituted tetrahydrofurans from the reaction of a vicinal t-butyldiphenylsilylmethyl-substituted cyclopropyl diester with aldehydes and ketones has been developed. The 2,5-cis-disubstitution predominates over the 2,5-trans-disubstitution by as much as 12:1. The reaction with cyclic ketones generates spiro-fused tetrahydrofurans in good yields.     

A Molecularly Defined Iron‐Catalyst for the Selective Hydrogenation of α,β‐Unsaturated Aldehydes

A selective iron‐based catalyst system for the hydrogenation of α,β‐unsaturated aldehydes to allylic alcohols is presented. Applying the defined iron–tetraphos complex [FeF(L)][BF₄] (L=P(PhPPh₂)₃) in the presence of trifluoroacetic acid a broad range of aldehydes are reduced in high yields using low catalyst loadings (0.05–1 mol %). Excellent chemoselectivity for the reduction of aldehydes in the presence of other reducible moieties, for example, ketones, olefins, esters, etc. is achieved. Based on the in situ detected hydride species [FeH(H₂)(L)]⁺ a catalytic cycle is proposed that is supported by computational calculations.     

REDUCTION OF CARBONYL COMPOUNDS TO THE CORRESPONDING ALCOHOLS WITH ISOPROPANOL ON DEHYDRATED ALUMINA UNDER MICROWAVE IRRADIATION

ABSTRACT

The reduction of different types of aldehydes and ketones were performed in the presence of isopropylalcohol (as solvent and hydride source) under microwave irradiation. It is proved that dehydrated Woelm chromatographic alumina supported KOH catalyses these transformations. Regioselectivity was observed in the reduction of cinnamaldehyde and chemoselectivity was observed in the reduction of carbonyl in the presence of nitro group.     

tert-Butyl esters of tripeptides based on Pro-Phe as organocatalysts for the asymmetric aldol reaction in aqueous or organic medium

The enantioselective aldol reaction between ketones and aldehydes constitutes one the most common reaction models for the evaluation of novel organocatalysts. The last few years, it has been shown that the organocatalytic aldol reaction can be performed in water. A family of tripeptides consisting of proline, phenylalanine, and tert-butyl esters of amino acids was successfully employed in this asymmetric transformation. The products of the reaction between various ketones and aldehydes were obtained in high yields (up to 99%) with excellent diastereo- (up to 97:3 dr) and enantioselectivities (up to 99% ee). The C-terminal amino acid determines the ability of the tripeptide (Pro-Phe-AA-O^tBu) to act efficiently in aqueous or organic medium.     

Synthetic applications of the tandem aldol condensation-radical cyclization sequence. A new and highly convergent method for the annulation of carbocycles

The sequential treatment of α,β-unsaturated ketones with (phenylseleno)alanes or titanates followed by representative β,γ-unsaturated aldehydes has been shown to furnish β-(phenylseleno)ketols in high yield. The reductive cyclization of these species in the presence of tri-$\text{n}$-butyltin hydride affords the corresponding condensed carbocycles with high efficiency.     

Enantioselective hydrosilylation of prochiral ketones catalyzed by chiral BINAP-copper(I) complexes

The CuCl/NaOt-Bu/BINAP system was found to efficiently catalyze the hydrosilylation of aryl alkyl ketones with excellent enantioselectivities by using phenyl methyl silane as a stoichiometric hydride source. High enantiomeric excesses (up to 97%) and excellent yields (up to 99%) were obtained.     

Stereocontrol in hydride addition to ketone-derived chiral N-acylhydrazones

Chiral N-acylhydrazones derived from various aldehydes and N-amino-4-benzyl-2-oxazolidinone have previously been shown to be effective for acyclic stereocontrol of intermolecular radical and allylsilane additions. Treatment of the propionaldehyde hydrazone with tributyltin hydride in the presence of boron trifluoride etherate led to rapid chemoselective reduction of the imine bond in high yield. Preparation of similar hydrazones from ketones led to E/Z isomer mixtures, usually in ratios of 4:1 or greater. Geometry of the CN bond was assigned by steric compression shifts in ¹³C NMR spectra. Reduction with tributyltin hydride and boron trifluoride etherate afforded diastereomer mixtures in ratios very similar to the original E/Z isomer ratios. The chiral auxiliary blocked the opposite face of the CN bond relative to a related process using a chelated Lewis acid. A stereocontrol model involving monodentate interaction of the N-acylhydrazone and boron trifluoride is consistent with the observed stereochemical outcome.     

Synthesis of 3-substituted 2-cyclohexenones through umpoled functionalization

A new protocol to obtain 3-substituted 2-cyclohexenones, was developed by reversing the chemical reactivity of 2-cyclohexenone. One-pot synthesis of 3-substituted 2-cyclohexenones can be achieved by treatment of 3-phenylthiosilyl enol ether with a mixture of t-BuLi/HMPA that allows hydrogen-selective exchange in presence of reactive electrophiles such as aldehydes, ketones and alkyl halides. This affords the corresponding product in moderate overall yield, after silyl enol ether cleavage and concomitant thiophenol elimination initiated with TBAF.     

A preparation of bromoolefins from carbonyl compounds

A variety of 1-bromoalkenes are prepared by addition of dibromomethyllithium to ketones and aldehydes followed by reductive elimination with zinc-acetic acid. The product E/Z ratios were determined, and halogen-lithium exchange with t-butyllithium was examined.     

1,4-Addition of an aryllithium reagent to diethyl ketomalonate. Scalable synthesis of ethyl 1-(hydroxymethyl)-1,3-dihydroisobenzofuran-1-carboxylate

While optimizing the synthesis of pharmaceutical building block 3 [ethyl 1-(hydroxymethyl)-1,3-dihydroisobenzofuran-1-carboxylate], we encountered an unusual addition of an aryllithium reagent to the ketone oxygen atom of diethyl ketomalonate. Compound 3 was ultimately prepared on a large scale by a two-step sequence involving (1) annulation of a functionalized Grignard reagent with diethyl ketomalonate and (2) selective mono-reduction of a geminal diester using lithium tri-tert-butoxyaluminum hydride.     

New synthesis of t-butyl arylpropiolates using diazo(trimethylsilyl)methylmagnesium bromide

Diazo(trimethylsilyl)methylmagnesium bromide smoothly reacted with t-butyl aryl(oxo)acetates to afford the corresponding arylpropiolates via alkylidenecarbene intermediates. In this reaction system, the magnesium bromide salt of trimethylsilyldiazomethane was significantly efficient compared to the lithium one, commonly known as a reagent for the conversion of aldehydes and aryl ketones into acetylenes.     

Novel tandem reactions of ethyl acetoacetate with aromatic aldehydes: product- and stereo-selective formation of highly functionalised cyclohexanones

The five-component tandem reaction of ethyl acetoacetate with aromatic aldehydes in the presence of pyrrolidine affords t(3),t(5)-diaryl-t(4)-[(E)-3-aryl-2-propenonyl]-r(2)-ethoxycarbonylcyclohexanones stereoselectively in good yields presumably via a tandem Knoevenagel condensation-Michael addition-condensation via enamine-deethoxycarbonylation-Michael addition sequence. The same reactants in the presence of DBU led to the formation of t(3)-aryl-r(2),c(4)-bisethoxycarbonyl-c(5)-hydroxy-t(5)-methylcyclohexanones in excellent yields via a tandem Knoevenagel condensation-Michael addition-aldol reaction sequence.     

Bu4NI-catalyzed α-acyloxylation reaction of ethers and ketones with aldehydes and tert-butyl hydroperoxide

The reaction of (hetero)aromatic aldehydes or cinnamaldehyde with di-/multi-ethers in the presence of Bu₄NI and tert-butyl hydroperoxide generated corresponding α-acyloxy ethers. Reactions between (hetero)aromatic aldehydes or cyclohexanecarbaldehyde with arylalkyl ketones under similar conditions resulted in α-acyloxy ketones. Collectively, Bu₄NI-catalyzed α-acyloxylation reactions exhibit a broad scope of substrates and a high compatibility with functional groups.     

Synthesis of sterically hindered ketones from aldehydes via O-silyl oximes

A mild and efficient method to synthesize sterically hindered ketones from aldehydes via O-silyl oximes was developed. Treatment of O-triphenylsilylated oximes with alkyl iodides in the presence of triethyl borane afforded the corresponding ketones.