Reaction of Unsaturated Esters with the Oxidative System Aluminum Tri-tert-Butoxide-tert-Butyl Hydroperoxide

Unsaturated esters containing double bonds in the acyl (methyl acrylate) or in the alcohol (vinyl and allyl acetates) fragments are cleaved under mild conditions (20°C) by the system aluminum tri-tert-butoxide-tert-butyl hydroperoxide to give tert-butyl esters of peroxycarboxylic acids and unsymmetrical aluminum alkoxides. The double bond in the acyl fragment is inert to this oxidation system. Vinyloxy- and allyloxy derivatives are oxidized to hydroxyethanal and (hydroxymethyl)oxirane, respectively. Carbonhydrogen bonds are oxidized only in allyl acetate.     

New reagent for the introduction of Boc protecting group to amines: Boc-OASUD

A new reagent, tert-butyl (2,4-dioxo-3-azaspiro [5,5] undecan-3-yl) carbonate (Boc-OASUD) for the preparation of N-Boc-amino acids is described. The Boc-OASUD reacts with amino acids and their esters at room temperature in the presence of a base and gives N-Boc-amino acids and their esters in good yields and purity. Introduction of the Boc group takes place without racemization. The Boc-OASUD, being a solid and more stable, is a better alternative to di-tert-butyl dicarbonate which is low melting and has to be dispensed in plastic containers than glass because of its poor stability.     

Enantioselektive α-Alkylierung von Asparagin- und Glutaminsäure über die Dilithium-enolatocarboxylate von 2-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]essigsäure und 3-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]propionsäure

Overall Enantioselective α-Alkylation of Aspartic and Glutamic Acid through Dilithium Enolatocarboxylates of 2- [3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]acetic and 3-[3-Benzoyl-2-(tert-butyl)-1-methyl-5-oxoimidazolidin-4-yl]propionic Acid, respectively The pure methyl esters 10 of the heterocyclic carboxylic acids specified in the title were prepared in several steps by known methods from aspartic and glutamic acid, with overall yields of ca. 20%. The corresponding heterocyclic acids 11 were doubly deprotonated by LiNEt₂/BuLi or LiN(i-Pr)₂/BuLi to give enolatocarboxylates ( 3 ). The latter were reacted with electrophiles (MeOD, Mel, C₆H₅CH₂Br) to give the crystalline products 14 – 21 diastereoselectively. Hydrolysis of the imidazolidinone ring of three such products gave the corresponding α-branched aspartic and glutamic acids 22 – 24 of known absolute configuration, thus establishing the stereochemical course of the overall enantioselective alkylations.     

Oxidation of β-dicarbonyl compounds with tert-butyl hydroperoxide in the presence of vanadyl acetylacetonate

Oxidation of β-dicarbonyl compounds with tert-butyl hydroperoxide in the presence of vanadyl acetylacetonate (benzene, 20°C) involves the activated methylene group with intermediate formation of trioxo derivatives and is accompanied by decomposition of carbon skeleton. The oxidation products are carbon dioxide, carboxylic acids, and tert-butyl and peroxy esters derived from the latter.     

A fast and practical synthesis of tert-butyl esters from 2-tert-butoxypyridine using boron trifluoride·diethyl etherate under mild conditions

A practical direct preparation of tert-butyl esters from 2-tert-butoxypyridine has been developed. This system features the use of boron trifluoride·diethyl etherate in toluene solvent to rapidly achieve the reaction at room temperature. Using this reaction protocol, a variety of tert-butyl esters were synthesized from several different carboxylic acids at high yields. This practical procedure provides a promising and effective approach to the protection of carboxylic acids with a tert-butyl group.     

Oxidation of Substituted 1,5-Hexadien-3-ols with Various Oxidants

Substituted 1,5-hexadien-3-ols were synthesized by the [2,3]-Wittig rearrangement of unsymmetrical bis-allyl ethers, as well as by reactions of 1-(2-alkenyl)-2-chloromethyloxiranes with Mg/THF. The products were oxidized with pyridinium chlorochromate (PCC), zinc chlorochromate (ZCC), tert-butyl hydroperoxide in the presence of OsO₄, and tert-butyl hydroperoxide alone. The oxidation of substituted 1,5-hexadien-3-ols with PCC and ZCC gave the corresponding carbonyl compounds. In the reaction with tert-butyl hydroperoxide catalyzed by OsO₄ the internal double bond in the substrate was regioselectively converted into epoxy group, whereas allylic oxidation was prevented.     

Enantioselective Syntheses of α-Amino Acids from 10-(Aminosulfonyl)-2-bornyl Esters and Di(tert-butyl) Azodicarboxylate. Preliminary Communication

Succesive treatment of chiral esters 1 with LiN(i-Pr)₂/Me₃SiCl and di(tert-butyl) azodicarboxylate/TiCl₄/Ti(i-PrO)₄ gave N,N′ -di[(tert-butoxy)carbonyl]hydrazino esters 9 which on deacylation, hydrogenolysis, transesterification, and acidic hydrolysis furnished (2S)-α-amino acids 6 in high enantiomeric purity with efficient recovery of the auxiliary alcohol 7 .     

Synthesis and cytotoxic activity of derivatives of the <Emphasis Type="Italic">tert</Emphasis>-butyl ester of 7<Emphasis Type="Italic">Z</Emphasis>-acetylmethylene-3-methyl-3-cephem-4-carboxylic acid

The condensation of the acetylmethylene group in the tert-butyl esters of 7Z-acetylmethylene-3-methyl-3-cephem-4-carboxylic acid and 7Z-acetylmethylene-3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid and in 7Z-acetylmethylene-3-methylene-1,1-dioxo-3-cephem with arylmethoxyamines and O-alkylation of the tert-butyl ester of 7Z-(2-hydroxyimino)propylidene-3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid using substituted benzyl bromides as well as pyridylmethyl chlorides gave arylmethoxyimino and pyridylmethoxyimino derivatives of these compounds in the syn and anti isomeric forms. The Vilsmaier reagent was used to introduce the N,N-dimethylaminomethylene group at C-2 of the cephem system in the tert-butyl esters of 7Z-[2-(arylmethoxyimino)propylidene]-3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid. Subsequent transformation of the N,N-dimethylaminomethylene cephems using hydroxylamine led to 3Z-[2-(anti-arylmethoxyimino)propylidene]-tert-butoxycarbonylmethyl-4-(5-methyl-4-isoxazolylsulfonyl)- azetidin-2-ones. Condensation of the acetyl group in the tert-butyl ester of 7Z-acetylmethylene- 3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid with 4-bromophenylhydrazine gave a cephem with a 2-(4-bromophenylhydrazono)propylidene group at C-7. Acylation of the tert-butyl ester of 7Z-(2-hydroxyimino)propylidene-3-methyl-1,1-dioxo-3-cephem-4-carboxylic acid by 2-bromobenzoyl chloride gave a cephem with a 2-(2-bromo-benzoyloxyimino)propylidene group at C-7. Biological screening of these products towards to malignant and normal cells in vitro showed that their antitumor activity and cytotoxic selectivity towards to malignant and normal cells depend on the structure and configuration of the arylmethoxyimino and pyridylmethoxyimino groups in the 7-alkylidene substituent as well as on the presence or absence of N,N-dimethylaminomethylene and carboxyl groups, respectively, at C-2 and C-4 of the cephem system.     

Improved Synthesis of Cyclic α-Hydrazino Acids of Five- to Nine-Membered Rings and Optical Resolution of 5,6,7-Membered Ring Hydrazino Acids

Synthesis of cyclic α-hydrazino acids of five- to nine-membered rings has been described. Di-tert-butyl or dibenzyl malonate was used as starting materials instead of diethyl malonate, which was used in our first report. Deprotection of tert-butyl or benzyl ester of the final compounds was much easier than that of ethyl or methyl esters. Overall yield of these acids were 39, 50, 47, 52, and 51%, respectively. These acids were then converted to the diastereomers either via the formation of peptides with L-phenylalanine methyl ester or via the formation of esters (for five- to seven-membered rings) with L-2-phenylalaninol. All diastereomers were separated except the nine-membered ring by flash chromatography. Hydrolysis of diastereomeric esters generated the optically pure five-, six- and seven-membered cyclic α-hydrazino acids. In this process, both the enantiomers have been isolated and the chiral auxiliary L-2-phenylalaninol was recovered. Absolute stereochemistry was determined from x-ray crystallographic analysis.     

Copolymerisation of maleic anhydride with electron-acceptor monomers

Copolymerisation of maleic anhydride with tert.-butyl methacrylate and trimethylsilyl methacrylate was studied. Both monomers form random copolymers with maleic anhydride and in both cases the acceptor monomer is incorporated preferentially into the copolymer. Maleic anhydride which does not homopolymerise has reactivity ratios of approximately zero. The esters have reactivity ratios of 12.8 for trimethylsilyl methacrylate and 2.95 for tert.-butyl methacrylate. Thermal behavior and molar masses were investigated as a function of composition. Conditions for hydrolysis of the trimethylsilyl ester groups to give free acid groups have been established.     

Transition metal free oxidative esterification of alcohols with toluene

Using Bu₄NI as the catalyst and tert-butyl hydroperoxide as the oxidant, direct esterification of alcohols with toluene derivatives was achieved. Mechanistic investigations indicate that the alcohols are sequentially oxidized to aldehydes, carboxylic acids, and then to benzyl esters. Bu₄N⁺ functions as a phasetransfer reagent and iodide catalyzes the reaction.     

Synthesis and Biological Properties of 3-(Dihydroxybenzoyloxy)methyl- and 3-(Diacetoxybenzoyloxy)methyl-7α-chlorocephalosporanate Sulfones

We describe the synthesis of tert-butyl esters of 3-(2-hydroxybenzoyloxy)methyl-, 3-(dihydroxybenzoyloxy)methyl-, and 3-(diacetoxybenzoyloxy)methyl-7-chlorocephalosporanic acid sulfones by reaction of tert-butyl ester of 3-bromomethyl-7-chlorocephalosporanic acid sulfone with salts of hydroxy- and acetoxy-substituted benzoic acids. We have investigated the elastase-inhibiting properties of the compounds obtained and also their in vitro cytotoxic activity.     

Synthesis and Phosphorylation of 2- and 3-Halomethyl Derivatives of Functionalized 2-tert-Butylfurans

2-Halomethyl derivatives of 3-functionalized 5-tert-butylfurans are phosphorylated underconditions of the Michaelis-Becker, Arbuzov reactions similarly to other halomethylfurans. No effectof the tert-butyl substituent on the yield of the reaction products was found in this case. Contrary to that, the2-methoxymethyl derivative of 3-chloromethyl-5-tert-butylfuran proved to be more thermostable than its analog containing no tert-butyl substituent. As a result, the yield of phosphonate in the Michaelis-Becker reaction under similar conditions increases 2.5 times. The observed stabilization of the furan ring is explained by shielding of its oxygen atom by the tert-butyl group.     

Alkylation of Imidazolidinone Dipeptide Derivatives: Preparation of Enantiomerically Pure Di- and Tripeptides by ‘Chirality Transfer’ via a Pivalaldehyde N,N-Acetal Center. Preliminary Communication

Glycylglycine, glycyl-(S)-alanine, and (S)-alanylglycine esters are cyclized through pivalaldehyde imines to give dipeptide-derived 3-(benzyloxycarbonyl)-2-(tert-butyl)-5-oxoimidazolidine-1-acetates 1 – 3 . These are alkylated diastereoselectively by Li-enolate formation and addition of alkyl bromides or iodides (products 4 – 6 ). Starting from (S)-alanine and glycine, (S)-alanyl-(S)-alanine or (R)-alanyl-(R)-alanine, and (R)-alanyl-(R)alanyl-(S)-alanine- have thus been prepared, with the (tert-butyl)-substituted N,N-acetal center playing the role of a pivot or lever for diastereoselective formation of new stereogenic centers under kinetic or thermodynamic control.     

The electronic effects of substituents at the acyl carbon in the gas-phase elimination kinetics of tert-butyl α-substituted acetates

The gas-phase eliminations of several tert-butyl esters, in a static system and in vessels seasoned with allyl bromide, have been studied in the temperature range of 171.5–280.1°C and the pressure range of 23–98 torr. The rate coefficients for the homogeneous unimolecular elimination of these esters are given by the following Arrhenius equations: for tert-butyl pivalate, log k₁(s^?1) = (13.44 ± 0.30) ? (169.1 ± 3.1) kJ · mol^?1 (2.303RT)^?1; for tert-butyl trichloroacetate, log k₁(s^?1) = (12.41 ± 0.08) ? (141.1 ± 0.7) kJ · mol^?1 (2.303RT)^?1; and for tert-butyl cyanoacetate log k₁(s^?1) = (11.31 ± 0.44) ? (137.8 ± 4.1) kJ · mol^?1 (2.303RT)^?1. The data of this work together with those reported in the literature yield a good linear relationship when plotting log k/k₀ vs. σ* values (ρ* = 0.635, correlation coefficient r = 0.972, and intercept = 0.048 at 250°C). The positive ρ* value suggests that the movement of negative charge to the acyl carbon in the transition state is rate determining. The present results along with previous investigations ratify the generalization that electron-withdrawing substituents at the acyl side of ethyl, isopropyl, and tert-butyl esters enhance the elimination rates, while electron-releasing groups tend to reduce them. The negative nature of the acyl carbon and the polarity in the transition state increases slightly from primary to tertiary esters.     

Element-Element-Bindungen. I. Synthese und Struktur des Tetra(tert-butyl)tetrarsetans und des Tetra(tert-butyl)tetrastibetans

Element-Element Bonds. I. Syntheses and Structure of Tetra(tert-butyl)tetrarsetane and of Tetra(tert-butyl)tetrastibetane Dilithium (tert-butyl)arsenide reacts with (tert-butyl)dichloroarsine to give tetra-(tert-butyl)tetrarsetane 1 ; homologous tetra(tert-butyl)tetrastibetane 2 is formed by reduction of (tert-butyl)dichlorostibane with magnesium. The isotypic compounds 1/2 crystallize in the monoclinic space group P2₁/c with Z = 4. The dimensions of the unit cells determined at ?45 ± 5°C are: a = 957.4(8)/1 000.2(3); b = 1 399.1(14)/1 423.9(4); c = 1 697.4(9)/1 749.8(7) pm; β = 96.02(6)/96.77(3)°. As shown by low temperature X-ray structure determinations (3 531/3 232 symmetry independent reflections; R_g = 4.0/4.6%) the four membered rings E₄ (E = As or Sb) are folded; in all-trans configuration the bulky organic substituents occupy pseudo-equatorial positions. Characteristic averaged bond distances and angles are: E? E 244/282; E? C 202/221 pm; ? E? E? E 86/85° ? E? E? C 101/99°. The dihedral angels of the bisphenoides built up by the atoms of the rings are found to be 139/133°.     

Generation and Reactions of Lithiated tert-Butyl and 2,6-Di(tert-butyl)-4-methylphenyl Cyclopropanecarboxylates

tert-Butyl and 2,6-di(tert-butyl)-4-methylphenyl (BHT) cyclopropanecarboxylates ( 4 , 6 , 24 , 25 ) are lithiated with LiN(i-Pr)₂ and t-BuLi, respectively. Reactions with alkyl halides, aldehydes, acyl chlorides, and heteroelectrophiles give α-substituted BHT esters which can be cleaved (t-BuOK/H₂O/THF) to the corresponding carboxylic acids or reduced (LiAlH₄/THF) to the cyclopropanemethanols.     

Synthesis of Enantiomerically Pure D- and L-(Heteroaryl)alanines by asymmetric hydrogenation of (Z)-α-amino-αβ-didehydro esters

Homogeneous asymmetric hydrogenation of a wide range of methyl and tert-butyl (Z)-2-(acylamino)-3-(heteroaryl)acrylates (see 1a–f and 2a–d, f, g , resp.) catalyzed by diphosphinerhodium catalysts was studied for the synthesis of enantiomerically pure 3-furyl-, 3-thienyl-, and 3-pyrrolylalanines (see 3a–f , and 4a–d, g ; Scheme 1). The precursors, the (Z)-α-amino-α,β-didehydro esters 1a–f and 2a–d, f, g were prepared in high yields using the phosphorylglycine-ester method (Scheme 1). Isomerically pure (Z)-α-amino-α,β-didehydro esters were required to obtain the highest enantiomeric excesses (ee's) in the asymmetric hydrogenation, and the tert-butyl-ester strategy was beneficial in terms of both getting pure (Z)-α-amino-α,β-didehydro esters and obtaining high ee's in the hydrogenation. Finally, in contrast to the methyl-ester series, deprotection of the tert-butyl esters 4a–d, g was easily performed using CF₃CO₂H without any racemization.     

Indium(III) chloride-catalyzed oxidative cleavage of carbon-carbon multiple bonds by tert-butyl hydroperoxide in water—a safer alternative to ozonolysis

An efficient and general method for the oxidative cleavage of alkenes and alkynes using tert-butyl hydroperoxide and indium(III) chloride as catalyst in water to give the corresponding carboxylic acids or ketones has been achieved. The reaction conditions are compatible with sensitive moieties such as peptide bonds, tert-butyl carboxylic esters and N-Boc-protected tryptophan. The catalyst could be recycled.     

Synthesis of 4-tert-butylperoxy-4-methylpentan-2-one and 3-tert-butylperoxy-3-methylbutanoic acid

Alkylation of tert-butyl hydroperoxide with 1,3-diols gave the corresponding hydroxy-containing ditertiary peroxides which were oxidized with pyridinium chlorochromate to carbonyl-containing peroxides. 3-tert-Butylperoxy-3-methylbutanal was oxidized with oxygen at room temperature to obtain 3-tert-butylperoxy-3-methylbutanoic acid.