Showing papers on "Alkylation published in 1988"

Chemical Chameleons. Organosulfones as Synthetic Building Blocks

Abstract: An overview of the duality of function of organosulfones as nucleophiles in basic media and electrophiles in Lewis acidic media, a change of reactivity for which they have been dubbed “chemical chameleons,” is presented. In the first phase, transition metal catalysts activate allyl sulfones towards displacements. Use of palladium, molybdenum, and nickel catalysts allow stabilized anions to effect displacement; copper catalysts allow non-stabilized nucleophiles to be used. The use of the anion stabilizing and leaving group abilities of sulfones created a novel three carbon intercalation and a novel cyclocontraction-spiroannulation in which β-hydroxy sulfones participate in a Lewis acid catalyzed pinacol rearrangement. The lability of allyl and tertiary sulfones towards Lewis acids creates a wide array of electrophilic reactions such as Friedel–Crafts type cyclizations, intermolecular alkylations with organoalanes and enol silyl ethers, and ring expansions. The ability to design novel reagents for synthesis...

Asymmetric synthesis catalyzed by chiral ferrocenylphosphine-metal complexes

Abstract: Optically active ferrocenylphosphines containing, on the side chain, hydroxy group appropriately distant from the ferrocene nucleus have been found to be effective ligands for the palladium-catalyzed asymmetric allylic alkylation of 1,3-disubstituted 2-propenyl acetates with sodium acetylacetonate and related soft carbon nucleophiles to give the alkylation products of up to 96% ee. chiral ferrocenylphosphines which have tertiary amines on the side chain have been found to catalyze the reaction of methyl isocyanoacetate with aldehydes in dichloromethane to give optically active trans-4-methoxy- carbonyl-5-alkyl-2-oxazolines with high enantioselectivity (up to 98% ee) in a quantitative yield.

Acidities of glycine Schiff bases and alkylation of their conjugate bases

Abstract: Equilibrium acidities in Me2S0 are reported for six ketimines of the type Ph2C=NCH(R)C02Et and five aldimines, ArCH=NCH(R)C02Et. Changing R in the ketimine from H to Ph increased the pKa by 2.2 units. This surprising acidity decrease for Ph substitution points to a substantial increase in steric effect, as do the increases in pKa of 3.8 and 4.2 units observed for the replacement of hydrogen by Me and PhCH,, respectively. Phase-transfer alkylation of the Ph2C=NCH2C02Et ketimine gave over 90% of monoalkylate whereas, under similar conditions, the aldimine 4-ClC6H4CH=NCH2C02Et gave a mixture of monoand dialkylate. The difference is that the pKa of the monoalkylated aldimine is essentially the same as that of the parent, which leads to rapid equilibration with the parent anion and consequent dialkylation. The rates of alkylation in Me2S0 of these parent and monoalkylated anions did not differ greatly, showing that the relative pKHAs of the parent acid and its monoalkyl derivative, rather than the relative rates of the monoand dialkylation reactions, is the principal factor that determines the extent of the competition between monoalkylation and dialkylation.

Enantioselective alkylation of carbonyl compounds. From stoichiometric to catalytic asymmetric induction

Abstract: Multinuclear organometallic species play a significant role in alkylation of carbonyl compounds. Enantioselective alkylation of aldehydes using a 1: 1 reagent/substrate stoichiometry is achievable by chirally modified lithium/magnesium binary organometallic reagents. For example, diethylmagnesium treated with di-O-lithio-(S)-2.2'- dihydroxy- 1, 1'-binaphthyl reacts with benzaldehyde in a THF- dimethoxyethane mixture at -100 OC to give (S)- 1-phenyl- 1- propanol in 92% ee. In the presence of a catalytic quantity of (4-3- exo-(dimethy1amino)isoborneol (DAIB), reaction of dialkylzincs and aldehydes in nonpolar media is accelerated greatly to lead to the corresponding S alcohols in very high enantiomeric excesses (up to 99% ee). The enantioselective catalysis involves fluxional organozinc species and the product-forming dinuclear intermediate possesses DAIB auxiliary, an aldehyde ligand, and three alkyl groups, where it is the bridging alkyl group, rather than the terminal alkyls, that migrates from zinc to the carbonyl carbon.

Diastereoselektive Alkylierung von 3‐Aminobutansäure in der 2‐Stellung

Abstract: Diastereoselective Alkylation 3-Aminobutanoic Acid in the 2-Position The enantiomerically pure 3-aminobutanoic acids (R)- and (S)-6 are readily available by preparative HPLC separation of the two diastereoisomers 5 obtained from addition of (S)-phenethylamine to methyl crotonate and subsequent hydrogenolysis (Scheme 2). (S)-Methyl 3-(benzoylamino) butanoate ((S)-3) is also available by enzymatic kinetic resolution with pig-liver esterase. The N-benzyl- and N- benzyloxycarbonyl derivatives rac3,8, and 9 of 3-aminobutanoates are doubly deprotonated with LDA and alkylated or aminated in high selectivity (17 examples, relative topicity like; see Tables 1 and 2). The configuration of three of the products is assigned (Schemes 4–6), and in four cases, the free α-substituted β-amino acid is prepared by acidic hydrolysis (see Table 3). It is shown that the doubly lithiated β-amino-acid derivative is solubilized, and its reactivity may be strongly influenced by the presence of 3 equiv. of LiCl.

Triply convergent synthesis of (-)-prostaglandin E2 methyl ester

Abstract: Synthese de l'ester methylique de la prostaglandine PGE2 a partir du cyclopentadiene via une dihydroxy-4,5 cyclopentene-2one

Albumin adsorption on alkyl chain derivatized polyurethanes: I. The effect of C‐18 alkylation

Abstract: The initial adsorption rate of delipidized Human Serum Albumin (HSA) is increased by addition of C-18 alkyl chains to a poly-urethane. The presence of alkyl chains does not appear to influence the total amount of HSA adsorbed after one hour exposure to a 5.0 mg/mL HSA solution. Neither does the desorption following one hour of adsorption appear to be influenced by the presence of alkyl chains. A study of the effects of solution concentration and temperature showed that the initial adsorption rates on both polymers are proportional to the protein concentration raised to the 0.36 power, and that alkylation of the polymer increases the activation energy of the initial adsorption rate above the 14 kJ/mol observed for the underivatized polyurethane. A new technique is presented to quantify the mass of adsorbed protein using Fourier transform infrared spectroscopy and attenuated total reflection optics. This technique uses the absorbance of bulk protein as an internal calibration reference, and appears to be as accurate and perhaps more precise than radiolabeling techniques.

General method for the asymmetric synthesis of α-amino acids via alkylation of the chiral nickel(II) Schiff base complexes of glycine and alanine

Abstract: Nickel(II) complexes of Schiff bases derived from (S)-o-[(N-benzylprolyl)amino] benzaldehyde and alanine (3), or (S)-O-[(N-benzylpropyl)amino]benzophenone and alanine (4), or glycine (5) have been used for the asymmetric synthesis of α-amino acids under a variety of conditions. The method of choice consists of the reaction of the corresponding complex with the appropriate alkyl halide in DMF at 25 °C using solid NaOH as a catalyst. Low diastereoselective excess (d.e.) is observed for the alkylation of complex (3) with benzyl bromide and allyl bromide. Large selectivity (80%) is observed for the alkylation of complex (4). Optically pure (R)- and (S)-α-methyl-α-amino acids [(S)-α-methylphenylalanine, (S)-α-allylalanine and (S)-O-benzyl-α-methyltyrosine] were obtained (70–90%) after the alkylated diastereoisomeric complexes had been separated on SiO2 and hydrolysed with aqueous HCl. The initial chiral reagents were recovered (80–92%). The alkylation of complex (5) gave (S)-alanine, (S)-valine, (S)-phenylalanine, (S)-tryptophan, (S)-isoleucine, (S)-2-aminohexanoic acid, and 3,4dimethoxyphenylalanine with optical yields of 70–92%. The optically pure α-amino acids were obtained after the separation of the alkylated diastereoisomeric complexes on SiO2. The stereochemical mechanism of the alkylation reaction is discussed.

Process for alpha-c-alkylation of the 8-acyl group of mevinolin and analogs thereof

Abstract: A process for alkylating the alpha position of the 8-acyl side chain in mevinolin and analogs thereof is disclosed. The process proceeds with a single charge of base and alkyl halide to give products with a pharmaceutically acceptable purity.

Diastereoselective alkylation of 3-acylimidazolidin-2-ones: synthesis of (R)- and (S)-lavandulol

Abstract: Alkylation en 2' du groupe acyl-3 par des hydrocarbures halogenes; scission reductrice par LiAlH 4 du substituant en 3. De cette facon synthese des (+)- et (−)-lavandulols de methyl-2 decanol-1 et de β-methyl benzenepropanol

Protein reactions with methyl and ethyl vinyl sulfones.

Abstract: Disulfide bonds of bovine serum albumin and wool were reduced by n-tributylphosphine to sulfhydryl groups that were then modified by methyl or ethyl vinyl sulfone in a nucleophilic addition reaction to S-(beta-ethylsulfonylmethyl)-L-cysteine and S(beta-ethylsulfonylethyl)-L-cysteine, respectively. The reductive alkylation was carried out either simultaneously, with both the reducing and alkylating agents present in the reaction mixture, or sequentially, with the reduced proteins first isolated before alkylation. Amino acid analysis studies showed that authentic, synthetic S-(beta-ethylsulfonylethyl)-L-cysteine eluted as a well-resolved peak after serine but that the peak associated with the corresponding methyl derivative overlapped the corresponding peak due to threonine. The extent of alkylation of the sulfhydryl groups of cysteine, epsilon-NH2 of lysine, and NH groups of the imidazole ring of histidine was also measured by amino acid analysis. The results show that alkyl vinyl sulfones have a strong chemical affinity for protein functional groups.

Structure and reactivity of lithium diphenylamide. Role of aggregates, mixed aggregates, monomers, and free ions on the rates and selectivities of N-alkylation and E2 elimination

Abstract: Rate studies of the N-alkylation of lithium diphenylamide with n-butyl bromide in THF/hydrocarbon mixtures (THF = tetrahydrofuran) are described. Dramatic induction periods observed for the N-alkylation at low THF concentrations are ascribed to the intervention of reactive mixed dimers of lithium diphenylamide and lithium bromide. In the presence of 1 .O equiv of added lithium bromide, the alkylation rate exhibits a first-order dependence on both the mixed aggregate and n-butyl bromide concentrations, supporting a pathway involving direct mixed aggregate alkylation. Incremental changes in the THF concentration uncovered contributions from several additional species. Regions of first or higher order followed by zero-order dependence on the THF concentration are interpreted as an equilibrium shift to a more reactive, highly solvated species assigned as a monomer (or ion pair). At elevated THF concentrations, the alkylation rate increases sharply as a function of the THF concentration, indicating the contribution of an additional, highly solvent dependent alkylation pathway. This latter pathway exhibits fractional-order dependence on the amide concentration, approximate first order dependence on the n-butyl bromide concentration, and a seventh-order dependence on the THF concentration. Common ion rate inhibitions by lithium perchlorate and lithium tetraphenylborate, a significant dependence on dielectric effects, and the observed reaction orders implicate a mechanism involving predissociation of free lithium ions. The appearance of competitive eliminations of the n-alkyl bromides to form 1-alkenes coincides with the appearance of the free ion alkylation pathway.

Benzothiopyranoindazoles, a new class of chromophore modified anthracenedione anticancer agents. Synthesis and activity against murine leukemias.

Abstract: The synthesis of the benzothiopyranoindazoles, a new class of chromophore modified anthracenediones related to mitoxantrone, is described In this structural class the quinone moiety, which is believed to be responsible for the cardiotoxicity of the anthracyclines, has been designed out The synthesis of the benzothiopyranoindazoles was carried out by a multistep sequence from requisite 1-chloro-4-nitro-9H-thioxanthen-9-one precursors Reaction with a monoalkylhydrazine gave a 5-nitrobenzothiopyranoindazole adduct, which was catalytically reduced to a corresponding C-5 anilino intermediate Alkylation of 7 with a requisite X(CH2)nNR1R2 (X = Cl, Br; R1, R2 = H, alkyl, acyl; n = 2,3) provided target "two-armed" benzothiopyranoindazoles or A-ring methoxy and/or side chain acyl intermediates, which could be converted to 3 by appropriate deprotection methodologies Alternatively, certain target compounds 3 were synthesized by reaction of 7 with appropriately functionalized glycine precursors under Schotten-Bauman or BOP chloride condensation conditions to provide C-5 acylamino intermediates, followed by Red-Al reduction and deprotection steps Described also is the synthesis of selected benzothiopyranoindazole congeners with proximal acylamino side chains at C-5 and B-ring sulfone functionality at S-6 Potent activity was demonstrated against murine L1210 leukemia in vitro (IC50 = 10(-7)-10(-9) M) as well as against P388 leukemia in vivo over a wide range of structural variants In general, activity against the P388 line was maximized by (a) a basic side chain at N-2 and a dibasic side chain at C-5 with primary or secondary distal amine substitution, (b) certain patterns of A-ring hydroxylation with 8-OH and 9-OH most favorable, and (c) sulfide oxidation state at S-6 Besides having curative activity against the P388 line, the more active compounds were curative against murine B-16 melanoma in vivo On the basis of their exceptional broad-spectrum in vivo anticancer activity, selected compounds in this series have been chosen for development toward clinical trials

Preparation and catalytic activity of a new solid acid catalyst

Abstract: The preparation and use of strong solid acid catalysts and superacids are active areas of research for isomerization, cracking, hydrocracking dehydration, alkylation, acylation, methanol to gasoline, etc. Because of the reported advantages of solid catalysts, recent research has focused on the preparation and characterization of stronger solid acids. In view of the higher activity associated with tetrahedral compared to octahedral aluminum Lewis acids, they are interested in preparing solids containing stable tetrahedral aluminum sites. In this paper they report the synthesis, characterization, and catalytic activity for these new solid acid catalyst systems.

A model for the diastereofacial differentiation in the alkylation of endocyclic enolate

Abstract: Alkylation des enolates de lithium de perhydro pyrannones-2 disubstitues en position 3 et 4

Identification of alkylation products of styrene oxide in single- and double-stranded DNA.

Abstract: Radioactive styrene oxide was reacted with double- and single-stranded DNA and the binding products were characterized by HPLC after neutral hydrolysis and enzyme digestion of DNA. More products were formed in single-stranded DNA as compared with double-stranded DNA. In single-stranded DNA at least 95% of the adducts were guanine N-7-,N2- and O6-alkylation products; they were formed in proportions 54:33:12. In double-stranded DNA the respective proportion was 74:23:3.7, indicating a selective suppression of alkylation at atoms N2 and, particularly, O6 that take part in hydrogen bonding in double-stranded DNA. The alpha- and beta-isomers of 7-alkylguanine were formed in a similar proportion in single- and double-stranded DNA, indicating no steric hindrance.