Benzyl Carbamate Research Articles

Catalyst‐Controlled Wacker‐Type Oxidation of Protected Allylic Amines

Catalyst‐Controlled Wacker‐Type Oxidation of Protected Allylic Amines

ChemInform Abstract: New Route to Optically Active Amine Derivatives: Ruthenium-Catalyzed Enantioselective Hydrogenation of Ene Carbamates.

Abstract The reaction of cyclic ketones with tert-butyl or benzyl carbamate under acidic conditions directly affords prochiral ene carbamates. Their enantioselective hydrogenation in the presence of a chiral ruthenium catalyst provides a new access to optically active carbamates easy to deprotect to the corresponding optically active amines.

ChemInform Abstract: Selective Hydrogenolysis of Novel Benzyl Carbamate Protecting Groups.

Highly efficient and selective hydrogenolysis of the 2-naphthylmethyl carbamate group (CNAP) in the presence of the 4-trifluoromethylbenzyl carbamate group (CTFB) has been observed for a wide range of substrates.

Pd-catalyzed one-pot chemoselective hydrogenation protocol for the preparation of carboxamides directly from azides

Abstract Carboxamides were obtained efficiently in high yields from azides on reaction with the corresponding pre-formed activated carboxylic acids in a single-step reductive transformation using hydrogen atmosphere (balloon) under Pd/BaSO4 or Pd/CaCO3 catalysis. The method is highly chemoselective and compatible with extremely labile functional groups such as benzyl carbamates, benzyl ethers, benzyl esters, and olefins.

Soluble phenyl valerate esterases of hen sciatic nerve and the potentiation of organophosphate induced delayed polyneuropathy

Contrary to some organophosphorus esters (OPs), certain esterase inhibitors including sulfonyl halides, carbamates and phosphinates do not cause axonal neuropathy, but they may exacerbate traumatic and some chemical insults to axons. This phenomenon is referred to as the promotion/potentiation of axonopathies. We report here promotion studies of the organophosphate induced delayed polyneuropathy (OPIDP). This neuropathy correlates with inhibition/aging of neuropathy target esterase, but this enzyme is not the target of promotion. Soluble phenyl valerate (PV) esterases in peak I ( V 0) of hen sciatic nerve were analysed. When these activities were inhibited in vitro by a mixture containing mipafox – an OP that causes OPIDP – paraoxon and p-toluene sulfonyl fluoride – two esterase inhibitors that do not cause either neuropathy or promotion–, then the remaining activity was sensitive to classical promoters such as phenylmethane sulfonyl fluoride (PMSF) and phenylmethyl benzyl carbamate. This PV-activity was not inhibited in sciatic nerves of hens treated with di-isopropyl phosphorofluoridate, at a dose that causes OPIDP. When these birds were further dosed with PMSF a dose–response relationship was observed between inhibition of PV-esterases, as above defined, and the severity of clinical responses. These data suggest that the target of promotion is embraced in peak I ( V 0) of soluble proteins of hen sciatic nerve.

A new preparative method for the synthesis of diethyl 1-diazo-2,2,2-trifluoroethylphosphonate via an imino phosphonate

A preparative method for the synthesis of diethyl 1-diazo-2,2,2-trifluoroethylphosphonate from trifluoroacetic anhydride and benzyl carbamate via diethyl 1-benzyloxycarbonylimino-2,2,2-trifluoroethylphosphonate is developed. Optimum conditions for the chlorination of benzyl N-trifluoroacetylcarbamate with SOCl2—Py to afford the imidoyl chloride, phosphorylation of the latter under the conditions of the Arbuzov reaction, as well as diazotization of amino phosphonate with isopropyl nitrite are found.

Gold(I)-Catalyzed Tandem Reactions Initiated by Hydroamination of Alkynyl Carbamates: Application to the Synthesis of Nitidine

As a convenient and direct synthesis of 1,2-dihydroisoquinolines, the gold(I)-catalyzed intramolecular hydroamination of (2-alkynyl)benzyl carbamates has been developed. The reaction with cationic gold(I) complex [AuCl(PPh(3))/AgNTf(2)] proceeded at room temperature, giving the desired 6-endo adducts. The addition of alcohol efficiently promoted the reaction, and the amount of the catalyst could be reduced to 1 mol %. However, the alkynes bearing either an electron-deficient aryl group or an alkyl group resulted in predominant production of 5-exo adducts. In such cases, use of a bulky gold catalyst, AuCl[(o-biPh)((t)Bu)(2)P]Cl/AgNTf(2), improved the regioselectivity, giving the 6-endo adducts in better yields. Furthermore, the hydroamination of alkynyl carbamates bearing an acetal or enone was successfully applied to the concise synthesis of tetracyclic heterocycles such as nitidine via the single catalyst-mediated tandem cyclization which consists of a condensation or a Michael addition of the resulting enecarbamates.

Iodolactonization: Past and Present Examples

Commercially available iodine has played an important role in organic synthesis. The review describes the use of iodine in the synthesis of several iodolactones and lactones. The cyclization of nonconjugated unsaturated acids, diallyl- hydroxyacetic acids, benzyl carbamates, norbornene derivatives, aryl-allenoic acids, olefinic amides and γ-methallyl malonic acids with iodine leads to the formation of iodolactones. This article is dedicated to Mr. Victor Marcos Simon on the occasion of his 95th Birthday. Keywords: Iodolactonization, organic synthesis, lactones, benzyl carbamates, norbornene derivatives

Synthesis of new 7-azabicyclo[2.2.1]heptane derivatives

The synthesis of new 7-azabicyclo[2.2.1]heptane derivatives has been achieved in a four-step synthetic sequence, starting from readily available cyclohex-3-enecarboxylic acid, Curtius reaction, stereoselective bromination leading to major benzyl(cis-3,trans-4-dibromocyclohex-1yl)carbamates (amides or sulfonamides), followed by NaH-mediated intramolecular cyclization. The synthesis and free radical cyclization of precursors 4-7, as well as the synthesis of a conformationally constrained epibatidine analogue 3 exploiting the reactivity of the 7azabicyclo[2.2.1]hept-2-yl radical in intramolecular reactions, are described. The N-sulfonyl functional motif is the only one to afford a cyclized product when incorporated in the radical precursor.

Aziridination of C60 with Simple Amides and Catalytic Rearrangement of the Aziridinofullerenes to Azafulleroids

The selective formation of aziridinofullerene and azafulleroid, which are isomers of the fullerene derivatives-introduced N(1) unit, is achieved. The ionic aziridination is a very convenient and risk-free procedure compared with the conventional method with azides as nitrogen sources, and gives aziridinofullerenes from various readily available amides (carbamates, ureas, carboxamides, and phosphamides). For example, benzyl carbamate was chlorinated by tert-butyl hypochlorite (tert-BuOCl) and then reacted with C(60) in the presence of base to give N-benzyloxycarbonyl aziridinofullerene exclusively and without formation of its isomer, an azafulleroid. The reaction enabled the synthesis of functional fullerene derivatives having a trialkoxysilyl group and an amino acid moiety. Azafulleroids were obtained through the rearrangement of corresponding aziridinofullerenes by using the combination of a chloramine catalyst and MS4A. Among other chloramines used, chloramine B (CB) showed superior ability as a catalyst in the rearrangement. It was found that MS4A functions as a Lewis acid in the reaction.

Comprehensive Experimental and Theoretical Studies of Configurationally Labile Epimeric Diamine Complexes of α-Lithiated Benzyl Carbamates

Different primary benzyl-type carbamates were deprotonated by sec-butyllithium in the presence of a tert-leucinol-derived bis(oxazoline) ligand. The resulting configurationally labile epimeric complexes equilibrated and one diastereomer was strongly favored in the equilibria. After dynamic thermodynamic resolution, the complexes could be trapped with different classes of electrophiles to yield highly enantioenriched secondary benzyl carb­amates. The stereochemical course of the substitution reactions was elucidated. High-level quantum chemical investigations were performed and allowed a prediction of both the favored complex and the enantiomeric excess that could be expected within the reactions.

Cu(I)-catalyzed stereospecific coupling reactions of enantioenriched α-stannylated benzyl carbamates and their application

Enantioenriched α-stannylated benzyl carbamates were used in highly stereospecific coupling reactions employing Cu(I) as catalyzing transition metal. Acid chlorides and allyl bromide derivatives were used as electrophilic coupling partners. The reaction was applied in the synthesis of two highly enantioenriched indanoles and one enantioenriched tetraline via intramolecular cyclization reactions.

Intermolecular hydroamination of allenes with N-unsubstituted carbamates catalyzed by a gold(I) N-heterocyclic carbene complex.

Reaction of 2,3-pentadienyl benzoate with benzyl carbamate catalyzed by a 1:1 mixture of (NHC)AuCl and AgOTf in dioxane at 23 degrees C for 5 h led to isolation of (E)-4-(benzyloxycarbonylamino)-2-pentenyl benzoate in 84% yield as a single regio- and diastereomer. Gold(I)-catalyzed hydroamination was effective for a number of N-unsubstituted carbamates and a range of substituted allenes.

Pharmacological effects of a novel isosorbide-based butyrylcholinesterase inhibitor

Isosorbide-2-benzylcarbamate-5-benzoate, a novel butyrylcholinesterase inhibitor, shows interspecies variation in its inhibitory activity (IC 50 of 4.3 nM for human plasma butyrylcholinesterase, but 1.09 μM for mouse plasma butyrylcholinesterase). Stability studies revealed that this drug is resistant to hydrolysis by human plasma (no degradation in 1 h). However, it was found to undergo rapid degradation when incubated with mouse plasma or mouse liver homogenate, yielding benzyl carbamate and benzoic acid. The addition of the carboxylesterase inhibitor bis-(4-nitrophenyl) phosphate (BNPP) inhibited the degradation of the novel drug, indicating that it may be a substrate for both butyrylcholinesterase and carboxylesterase. The absence of carboxylesterase from human plasma explains the drug's stability in this medium. In vivo, pharmacodynamic studies on single doses of 1 mg/kg to naïve male C57BL/6 mice revealed maximal plasma butyrylcholinesterase inhibition 20 min after intraperitoneal administration (∼60% inhibition) and 1 h after administration by gavage (∼45% inhibition). While this plasma butyrylcholinesterase inhibition was short-lived, the drug also penetrated the blood–brain barrier resulting in a slight (10–15%) but persistent (≥72 h) reduction in brain butyrylcholinesterase activity.

Heteropoly acids: a green and efficient heterogeneous Brønsted acidic catalyst for the intermolecular hydroamination of olefins

Intermolecular hydroamination of non-activated olefins with amides and benzyl carbamate proceeds efficiently in the presence of environmentally benign silicotungstic acid (HSiW) catalyst under mild conditions in air to afford addition products in good to excellent yields.

Configurationally Labile Lithiated O -Benzyl Carbamates: Application in Asymmetric Synthesis and Quantum Chemical Investigations on the Equilibrium of Diastereomers

The absolute configuration of the lithium atoms in the epimeric (−)-sparteine complexes were assigned incorrectly. The correct absolute configuration of the lithium atoms within the energetically favored pair of complexes is S for both the (−)-sparteine complexes 14⋅11 and 20⋅11. The statements in which the absolute configuration of lithium is explicitly mentioned in the paragraph beginning “At first glance, the quantitative description…︁” on page 82 should read: “In the four diastereomeric complexes of 14⋅11, the pair of diastereomers with an S-configured lithium cation is energetically strongly favored, thus ruling out the pair of RLi-configured complexes. …︁ Again, one pair of diastereomers (SLi-configured) is clearly favored. Here, the SLi,RC-configured complex is favored.” The absolute configurations of the lithium atoms in Figure 2 and in the Supporting Information and the absolute configurations of the benzylic carbon atoms in Figure 2 are wrong. The correct assignments in Figure 2, from top down, are: (SLi,RC) 14⋅11 (SLi,SC), (SLi,RC) 20⋅11 (SLi,SC), (RC) 14⋅12 b (SC), (RC) 20⋅12 b (SC). The conclusions drawn remain valid.

Latrunculin A and Its C-17-O-Carbamates Inhibit Prostate Tumor Cell Invasion and HIF-1 Activation in Breast Tumor Cells

The marine-derived macrolides latrunculins A ( 1) and B, from the Red Sea sponge Negombata magnifica, have been found to reversibly bind actin monomers, forming a 1:1 complex with G-actin and disrupting its polymerization. The microfilament protein actin is responsible for several essential functions within the cell such as cytokinesis and cell migration. One of the main binding pharmacophores of 1 to G-actin was identified as the C-17 lactol hydroxyl moiety that binds arginine 210 NH. Latrunculin A-17- O-carbamates 2- 6 were prepared by reaction with the corresponding isocyanates. Latrunculin A ( 1) and carbamates 4- 6 displayed potent anti-invasive activity against the human highly metastatic human prostate cancer PC-3M cells in a Matrigel assay at a concentration range of 50 nM to 1 microM. Latrunculin A ( 1, 500 nM) decreased the disaggregation and cell migration of PC-3M-CT+ spheroids by 3-fold. Carbamates 4 and 5 were 2.5- and 5-fold more active than 1, respectively, in this assay with less actin binding affinity. Latrunculin A ( 1, IC 50 6.7 microM) and its 17- O-[ N-(benzyl)carbamate ( 6, IC 50 29 microM) suppress hypoxia-induced HIF-1 activation in T47D breast tumor cells.

The Reaction Mechanism of the Hydroamination of Alkenes Catalyzed by Gold(I)−Phosphine: The Role of the Counterion and the N-Nucleophile Substituents in the Proton-Transfer Step

The reaction mechanism of the gold(I)-phosphine-catalyzed hydroamination of 1,3-dienes was analyzed by means of density functional methods combined with polarizable continuum models. Several mechanistic pathways for the reaction were considered and evaluated. It was found that the most favorable series of reaction steps include the ligand substitution reaction in the catalytically active Ph3PAuOTf species between the triflate and the substrate, subsequent nucleophile attack of the N-nucleophile (benzyl carbamate) on the activated double bond, which is followed by proton transfer from the NH2 group to the unsaturated carbon atom. The latter step, the most striking one, was analyzed in detail, and a novel pathway involving tautomerization of benzyl carbamate nucleophile assisted by triflate anion acting as a proton shuttle was characterized by the lowest barrier, which is consistent with experimental findings.

Practical chemoenzymatic dynamic kinetic resolution of primary amines via transfer of a readily removable benzyloxycarbonyl group

A practical method for chemoenzymatic dynamic kinetic resolution of primary amines using dibenzyl carbonate as acyl donor has been developed leading to benzyl carbamates, which can be deprotected under very mild reaction conditions to give the free amine.

Configurationally Labile LithiatedO-Benzyl Carbamates: Application in Asymmetric Synthesis and Quantum Chemical Investigations on the Equilibrium of Diastereomers

The title compounds were generated by deprotonation of different benzyl-type carbamates with sec-butyllithium in the presence of chiral diamines (-)-sparteine or diisopropyl and di-tert-butyl bis(oxazoline)s. These lithiated species exhibit configurational lability at -78 degrees C. In the case of the chiral di-tert-butyl bis(oxazoline), the equilibrium of the epimeric complexes can be used synthetically to obtain highly enantioenriched secondary benzyl carbamates. The enantiodetermining step was proven to be a dynamic thermodynamic resolution. The absolute configurations of the products were determined, and the stereochemical pathways of selected substitution reactions were thus elucidated. High-level quantum chemical investigations were performed to gain insight into the experimentally investigated system. To obtain an accuracy for the energy difference (delta deltaH) between two epimeric complexes of about 0.5 kcal mol(-1) as well as the correct sign, a theoretical procedure was established. It included geometry optimization at the dispersion-corrected DFT level, computation of zero-point vibrational energies, and single-point SCS-MP2 energy calculations with large atomic-orbital basis sets.