Alkyl Transfer Reactions Research Articles

Stereoselective synthesis of ( Z)-fluoroalkenes directed to peptide isosteres: copper mediated reaction of trialkylaluminum with 4,4-difluoro-5-hydroxyallylic alcohol derivatives

Copper mediated alkyl-transfer reaction of trialkylaluminum (R 3Al) with ( E)-4,4-difluoro-5-hydroxyallylic alcohol derivative smoothly proceeded to give the corresponding 2-alkylated 4-fluoro-5-hydroxyhomoallylic alcohol derivative with completely Z and 2,5- syn selective manner. Regio- and stereoselective conversion of the C5-hydroxyl group of the fluoroolefin thus obtained to amino group could be achieved through one-pot mesylation and azidation reaction.

Cu(I)‐Mediated Alkyl Group Transfer of Alkylboranes to Carboxylic Acid Chlorides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Cu(I)-Mediated Alkyl Group Transfer of Alkylboranes to Carboxylic Acid Chlorides

The alkyl group transfer reaction of alkylboranes with carboxylic acid chlorides affords the corresponding ketones in moderate yields in the presence of potassium tertbutoxide and copper(I) iodide. We reported previously that the electrochemical alkyl group transfers from trialkylboranes to carbonyl compounds, carboxylic acid compounds and epoxide compounds by implementing an electrochemical procedure using copper as a sacrificial anode in an undivided cell. As soon as it was published, this method drew great attention because of its enormous potential in synthetic utility. Therefore, based on this method, we examined the alkyl group transfer reaction of alkylboranes with carboxylic acid chlorides by the electrochemical procedure and also by the general organic chemistry procedure. Now, we report a new methodology for the alkyl group transfer reaction of alkylboranes with carboxylic acid chlorides via the reactive copper(I) alkylborate complexes in the presence of potassium tert-butoxide and copper(I) iodide by a mild organic chemistry process. Although alkylmagnesium, -zinc, -tin, and aluminum reagents have been successfully used for alkyl transfer reactions with acid chloride, the result comprises an excellent carbon-carbon bond formation synthesis since alkylboranes are readily prepared by hydroboration from alkenes, unlike alkyl transfer reactions reported by Suzuki et al. And this reaction was also successful in carbon-carbon bond formation without expensive palladium catalysts. First of all, a variety of solvents, such as tetrahydrofuran (THF) hexamethylphosphoric triamide (HMPA) (1 : 1, 2 : 1, 5 : 1), tetrahydrofuran (THF) dimethylformamide (DMF) (2 : 1), and tetrahydrofuran (THF) as a solvent, copper(I) halides, such as copper(I) bromide, copper(I) iodide, and copper(I) chloride, and bases, such as potassium tert-butoxide, sodium methoxide, and sodium ethoxide were examined to find the combination that affords the best yield. As a result, we found that THF-HMPA (2 : 1) as a solvent, copper(I) iodide as a copper(I) halide, and potassium tertbutoxide as a base gave the best yield (Table 1). As shown in Table 1, the ethyl group transfer reaction of triethylborane was especially affected not by sodium methoxide (entry 9) and sodium ethoxide (entry 10) but by potassium tert-butoxide (entry 1). Also copper(I) halides

The MPEG effect: improving asymmetric processes by simple additives.

Small amounts of simple methoxy poly(ethylene glycol)s (MPEGs) have a beneficial effect on catalyzed asymmetric aryl and alkyl transfer reactions onto aldehydes. The enantiomeric excesses of the products are improved, and this "MPEG effect" allows a reduction of the catalyst loading by a factor of 10.

Stereoselective Construction of Functionalized (Z)‐Fluoroalkenes Directed to Depsipeptide Isosteres.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereoselective construction of functionalized ( Z)-fluoroalkenes directed to depsipeptide isosteres

Cu(I)-mediated alkyl-transfer reaction of trialkylaluminum (R 3Al) with ( E)- or ( Z)-4,4-difluoro-5-hydroxyallylic alcohol derivatives proceeded in an SN′-type manner to give the corresponding 2-alkylated ( Z)-4-fluoro-5-hydroxyhomoallylic alcohol derivatives with 2,5- syn- or 2,5- anti selectivity, respectively. Oxidation of the primary hydroxyl group of the product to carboxylic acid was easily achieved without epimerization at the chiral centers.

Catalyzed Asymmetric Arylation Reactions.

Addition and substitution reactions with carbon nucleophiles are fundamental processes in organic synthesis, and the development of general catalytic asymmetric variants thereof is still a major challenge today. In contrast to enantioselective alkyl transfer reactions, the corresponding arylations have not yet reached a high level of maturity. The existing protocols are either of no general applicability or are limited in terms of selectivity. This article summarizes established routes for catalytic asymmetric aryl transfer together with the latest developments in this area. The scope and limitations of this reaction are discussed.

Mechanistic studies on the alkyltransferase activity of serotonin N-acetyltransferase

Background: Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) catalyzes the first, rate-limiting step in the biosynthesis of the circadian hormone melatonin (5-methoxy- N-acetyltryptamine) from serotonin. Our recent discovery that, in addition to catalyzing the acetyl transfer from acetyl-coenzyme A (acetyl-CoASH) to serotonin, AANAT is also a robust catalyst for the alkyl transfer reaction between CoASH and N-bromoacetyltryptamine has not only opened up a new way to develop cell-permeable AANAT acetyltransferase inhibitors that are valuable in vivo tools in helping elucidate melatonin’s (patho)physiological roles, but has also raised a question – how does AANAT accelerate the alkyl transfer reaction? In this study, mechanistic aspects of the AANAT-catalyzed alkyl transfer reaction were explored by employing CoASH and a series of N-haloacetyltryptamines that were also evaluated for their AANAT acetyltransferase inhibitory activities. Results: Investigation of various N-haloacetyltryptamine analogs showed a similar leaving group effect on the enzymatic and non-enzymatic reaction rates. Steady-state kinetic analyses demonstrated that AANAT alkyltransferase obeys a sequential, ternary complex mechanism, with random substrate binding. Rate versus pH profiles revealed the catalytic importance of an ionizable group with p K a∼7. All those N-haloacetyltryptamines that serve as substrates of AANAT alkyltransferase are also potent (low micromolar) in vitro inhibitors against AANAT acetyltransferase activity. In particular, N-chloroacetyltryptamine was also shown to be a potent inhibitor of intracellular melatonin production in a pineal cell culture assay. Conclusions: This is the first detailed investigation of the alkyltransferase activity associated with an acetyltransferase. Our results indicate that AANAT does not accelerate the alkyl transfer reaction by simple approximation effect as previously proposed for the similar alkyl transfer reaction catalyzed by other acyltransferases. This study has general implications for developing novel inhibitors by taking advantage of the promiscuous alkyltransferase activity associated with several acyltransferases.

ChemInform Abstract: Electrochemical Alkyl Transfer Reactions of Trialkylboranes to Carbonyl Compounds by Use of Aluminum Sacrificial Anode.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Reactions of N-Methylated Amino Acids and Benzylammonium Ions with P73- and As73-: Unusual Stereospecific Alkyl Group Transfers in the Synthesis of R2P7- and R2As7- Ions

Ethylenediamine (en) solutions of E73-, where E = P (1) or As (2), react with excess (PhCH2)Me3NBr to give NMe3 and a single diastereomer of the (PhCH2)2E7- ions, where E = P (3) or As (4), in good yields. X-ray crystal structures of the [PPh4]3 and [K(2,2,2-crypt)]4 salts showed that both anions adopt the sterically favored symmetrical structure. DMF solutions of 1 also react with ethyl esters of N-methylated amino acids, (EtOCOCHR)Me3N+, where R = H (glycine) or Me (alanine), to give (EtOCOCHR)2P7- ions where R = H (7) or Me (8). The transfer of Me+ to give the known Me2P7- ion (5) is competitive with (EtOCOCHR)+ transfer when R is not a proton such that 5 is favored over the formation of 8 (5:8 = 2.5:1), but 5 is only a trace impurity for R = H (5:7 ≈ 1:48). Reactions of R and S enantiomers of the alanine esters were conducted to probe the stereochemistry at carbon in these reactions, but the three different diastereomers of 8 (i.e., (R,R)- or (S,S)-, (R,S)-, and (S,R)-(EtOCOCHR)2P7-) were indistinguishable by NMR spectroscopy. These studies advance the alkylation chemistry of the polypnictides by (1) unequivocally showing which isomer is formed in the alkyl transfer reaction, (2) showing that the alkylammonium alkylations proceed with As73- with the same stereospecificity, and (3) demonstrating that the chemistry can be extended to N-methylated amino acid esters. Crystallographic data for [PPh4]3: orthorhombic, space group Pbca, a = 17.6049(13) Å, b = 17.1910(12) Å, c = 23.798(2) Å, V = 7202.4(9) Å3, Z = 8, R(F) = 4.03%, R(wF2) = 10.41% (Fo > 4σFo). For [K(2,2,2-crypt)]4: monoclinic, space group I2/a, a = 25.527(2) Å, b = 13.292(2) Å, c = 24.687(2) Å, β = 96.836(11)°, V = 8317(2) Å3, Z = 8, R(F) = 6.47%, R(wF2) = 15.85% (Fo > 4σFo).

ChemInform Abstract: Electrochemical Alkyl Transfer Reactions of Trialkylborane to Carbonyl Compounds by Use of Copper Sacrificial Anode.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Electrochemical alkyl transfer reactions of trialkylborane to carbonyl compounds by use of copper sacrificial anode

Alkyl groups in trialkylboranes were successfully transferred to carbonyl compounds in the presence of the platinum cathode and copper anode by electrochemical method. The new, mild electrochemical alkyl transfer reaction produced various substituted alcohols in good yields.

A theoretical study of the methyl ligation in tetraaza macrocycle nickel complexes which model the acetyl-CoA synthase active site

Recently, great attention has been devoted to the study of structural and functional features of the Cluster A of CO dehydrogenase/acetyl-CoA synthase as well as of several synthetic complexes which may serve as model systems (S.W. Ragsdale and C.G. Riordan, J. Biol. Chem., 1 (1996) 489). It has been shown experimentally that all these systems are capable of performing alkyl transfer reactions, but a general consensus concerning the reaction mechanism has not yet been reached. The aim of this study was the theoretical investigation, by means of the Hartree-Fock (HF) method, of the methyl ligation reaction to tetraaza macrocycle nickel complexes. To this end, the Hartree-Fock computational approach was first tested by comparing its results with those obtained experimentally and using other theoretical approaches. Once demonstrated that, for this class of compounds. Hartree—Fock calculations produce structural and energetic data fairly accurately, the study was extended to the investigation of possible methyl ligation paths to the RRRR and RRSS configurational isomers of [Ni(cyclam)] complexes. These reactions are discussed considering the geometries of the nickel complexes which correspond to optimum ab initio structures as well as the associated reaction energies and electron and spin distribution. Our theoretical results indicate that (i) the methyl transfer reaction is highly unfavoured for Ni(II) complexes, (ii) the most probable mechanism of methyl ligation involves methyl radical transfer, in agreement with some proposals based on experimental observations, and (iii) the RRRR [Ni(cyclam)] isomer undergoes a more exothermic methyl ligation reaction with respect to the RRSS isomer. Furthermore, this difference in reactivity can be rationalized on the basis of steric and electronic effects, revising a previously proposed hypothesis.

Inhibition of human O6-alkylguanine-DNA alkyltransferase and potentiation of the cytotoxicity of chloroethylnitrosourea by 4(6)-(benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues.

A series of 4(6)-(benzyloxy)-2,6(4)-diamino-5-(nitro or nitroso)pyrimidine derivatives and analogues of which 4(6)-benzyloxy groups were replaced with a (2-, 3-, or 4-fluorobenzyl)oxy or (2-, 3-, or 4-pyridylmethyl)oxy group, was synthesized. The abilities of these compounds to inhibit human O6-alkylguanine-DNA alkyltransferase (AGAT) in vitro and to potentiate the cytotoxicity of 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl) -3-nitrosourea (ACNU) toward HeLa S3 cells were evaluated. 2,4-Diamino-6-[(2-fluorobenzyl)oxy]-5-nitropyrimidine (3) and 2,4-diamino-5-nitro-6-(2-pyridylmethoxy)pyrimidine (6), whose ortho positions of the 6-substituent are modified, were much weaker in terms of these abilities than the corresponding meta- or para-modified compounds. These results are consistent with those of our previous study using a series of O6-benzylguanine derivatives. All 5-nitrosopyrimidine derivatives examined exerted both stronger AGAT-inhibition and ACNU-enhancement abilities than the corresponding 5-nitro derivatives. Among a variety of compounds that we have examined to date, 2,4-diamino-6-[(4-fluorobenzyl)oxy]-5-nitrosopyrimidine (10) exhibited the strongest ability to inhibit AGAT, and its magnitude was 2.5 and 50 times those of 4-(benzyloxy)-2,6-diamino-5-nitrosopyrimidine (9) and O6-benzylguanine (1), respectively. A strong positive correlation was observed between the ability to inhibit AGAT and to potentiate the cytotoxicity of ACNU. This strongly indicates that 4(6)-(benzyloxy)pyrimidine derivatives and their analogues potentiate ACNU cytotoxicity by inhibiting AGAT activity. To characterize the reactivity of test compounds, alkyl-transfer reactions were also carried out using the biomimetic alkyl-transfer system.

Is a hydrogen-bonded carbene an intermediate in the organoaluminum-induced ring opening of pyranosides? ring opening of pyranosides?

Semiempirical and ab initio quantum chemical computations indicate that the intermediate formed prior to the selectivitydetermining methyl transfer step in the reaction between glycosides and trimethylamiuum is a strongly hydrogen-bonded equilibrium O···HCOH···C, which is proposed to be an important selectivity promoting factor in the alkyl transfer reaction.

Intermolecular Alkyl Transfer Reactions in the Fast Atom Bombardment Mass Spectrometry of Esters

Intermolecular Alkyl Transfer Reactions in the Fast Atom Bombardment Mass Spectrometry of Esters

Intermolecular Alkyl Transfer Reactions in the Fast Atom Bombardment Mass Spectrometry of Esters

Fast atom bombardment mass spectrometry (FABMS) of five neat phthalates (dimethyl, diethyl, diallyl, dibutyl and dinonyl) were investigated and intermolecular alkyl transfer reactions were observed in the mass spectra. FABMS of some related compounds was also studied and the results indicate that intermolecular alkyl transfers can occur in the FABMS of esters, the transferred alkyl group being associated with the carboxylate group in the adduct ion [M+R]+. A possible mechanism is proposed which suggests that the transalkylation reactions in these non-ionic compounds arise from two routes: (i) nucleophilic attack by the electron-rich moiety of one energized desorbed molecule on to the electron-poor moiety of another and (ii) dissociation of the internally excited desorbed molecules. The study also demonstrated that the transalkylation reaction could be effectively controlled by addition of a suitable matrix, such as 3-nitrobenzyl alcohol.

Reaction pathways for the aromatization of paraffins in the presence of H-ZSM-5 and Zn/H-ZSM-5

The effect of the dehydrogenating component of H-ZSM-5 and Zn/H-ZSM-5 catalysts on n-heptane aromatization reaction was studied. An increase in the yield of aromatics observed over Zn/H-ZSM-5 is explained by the enhanced production of olefins, facilitating the aromatization reaction by the effective dehydrogenating action of zinc on paraffins. A significant change in the selectivities of toluene and C 9+ aromatics was observed after addition of zinc. The increase in the yield of toluene observed over Zn/H-ZSM-5 from both n-heptane and Bombay High (BH) light naphtha indicates the possible occurrence of direct dehydrocyclization of paraffins in the presence of zinc. Zinc also facilitates the effective conversion of C 6–C 8 oligomers to the corresponding aromatics, an in that way suppresses the further oligomerization of C 6–C 8 oligomers on one hand, and cracking of C 6–C 8 oligomers on the other; which is reflected in the decreased yields of fuel gas and C 9+ aromatics in the product. The product pattern of the BH light naphtha aromatization suggests that the presence of zinc also suppresses the acid catalyzed alkyl transfer reactions which generally take place over H-ZSM-5. Reaction pathways have been established to explain the selectivity changes that occurred in presence of zinc.

ChemInform Abstract: Unexpected O → S and N → S Alkyl Transfer Reactions in the Reaction of 3‐Alkyl‐2‐(N‐cyanoimino)thiazolidines with Sodium Alkoxides: A New Synthesis of Cimetidine.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Alkyl-transfer reactions from transition metal alkyl complexes to CpFe(CO)2-: rate and mechanistic studies

We have examined reactions of several alkyl complexes (Mn(CO) 5 Me, Mn(CO) 5 CH 2 Ph, Mn(CO) 5 Ph, CpMo(CO) 3 Me, CpMo(CO) 3 Et, and CpMo(CO) 3 CH 2 Ph) with CpFe(CO) 2 - . Each of these reactions results in transfer of the alkyl group to the iron with formation of Mn(CO) 5 - or CpMo(CO) 3 -