Formation Of Silyl Enol Ethers Research Articles

Streamlining the Synthesis of Pyridones through Oxidative Amination of Cyclopentenones

AbstractHerein we report the development of an oxidative amination process for the streamlined synthesis of pyridones from cyclopentenones. Cyclopentenone building blocks can undergo in situ silyl enol ether formation, followed by the introduction of a nitrogen atom into the carbon skeleton with successive aromatisation to yield pyridones. The reaction sequence is operationally simple, rapid, and carried out in one pot. The reaction proceeds under mild conditions, exhibits broad functional group tolerance, complete regioselectivity, and is well scalable. The developed method provides facile access to the synthesis of 15N‐labelled targets, industrially relevant pyridone products and their derivatives in a fast and efficient way.

Streamlining the Synthesis of Pyridones through Oxidative Amination of Cyclopentenones.

Herein we report the development of an oxidative amination process for the streamlined synthesis of pyridones from cyclopentenones. Cyclopentenone building blocks can undergo in situ silyl enol ether formation, followed by the introduction of a nitrogen atom into the carbon skeleton with successive aromatisation to yield pyridones. The reaction sequence is operationally simple, rapid, and carried out in one pot. The reaction proceeds under mild conditions, exhibits broad functional group tolerance, complete regioselectivity, and is well scalable. The developed method provides facile access to the synthesis of 15N-labelled targets, industrially relevant pyridone products and their derivatives in a fast and efficient way.

Syntheses of 9‐Vinylated Benzotropolones by a Sequence of Acylation, Ring‐Closing Enyne Metathesis, and Oxidation

AbstractPrevious studies from our group revealed that 6,7‐benzannulated nona‐1,8‐diene‐5‐ones of a variety of substitution patterns undergo ring‐closing diene metatheses in the presence of the Grubbs‐II catalyst; the benzocycloheptadienones formed thereby gave benzotropolones in between one and four follow‐up steps. The present study discloses that exemplary 6,7‐benzannulated non‐1‐en‐8‐yn‐5‐ones undergo ring‐closing enyne metatheses in the presence of the Grubbs‐II catalyst; the vinylated benzocycloheptadienones formed thereby gave 9‐vinylbenzotropolones in four steps: silyl enol ether formation, Rubottom‐type oxidation, desilylation, and Dess‐Martin oxidation. The metathesis substrates were synthesized either from (ortho‐bromoaryl)ethynes with an unsubstituted sp‐carbon by a Br→Li exchange and an acylation with an H2C=CH‐containing Weinreb amide; or, they were synthesized from (ortho‐bromoaryl)ethynes with a trimethylsilylated sp‐carbon by a Br→Li→ZnHal exchange, an acylation with an H2C=CH‐containing thioester, and a desilylation.

Ligand-controlled cobalt-catalyzed remote hydroboration and alkene isomerization of allylic siloxanes.

The Co-catalyzed remote hydroboration and alkene isomerization of allylic siloxanes were realized by a ligand-controlled strategy. The remote hydroboration with dcype provided borylethers, while xantphos favored the formation of silyl enol ethers.

Enantioselective desymmetrisation of an epoxytropinone for peduncularine synthesis

A key 7-allyl-8-hydroxy-6-azabicyclo[3.2.1]octan-3-one intermediate in a synthesis of the alkaloid peduncularine is obtained enantioenriched, by desymmetrisation of an achiral 6,7-epoxy-8-azabicyclo[3.2.1]octan-3-one (epoxytropinone). Chiral lithium amide-assisted enantioselective silyl enol ether formation then TMSOTf/allyltrimethylsilane/2,6-lutidine-induced rearrangement−allylation proceeded in up to 80:20 er, but modest overall yield. Chiral amines or (thio)ureas replacing 2,6-lutidine gave up to 76:24 er directly from epoxytropinone. A direct, simplified (base-free) process using a BINOL-derived bis(sulfuryl)imide catalyst and allyltrimethylsilane proved the most promising (80%, 83:17 er).

First study of rhodium(I) complexes with chiral sulfur-containing terpenoids as catalytic systems for ketone hydrosilylation

Using a “chiral pool” approach, a number of chiral thiolate and sulfide ligands based on natural terpenes and terpenoids have been synthesized in a few simple steps. Two new Rh-thiolate complexes with the formula [Rh(CO)2(μ-SR)]2 were obtained. The influence of these complexes and catalytic systems formed by combining the synthesized ligands with [Rh(CO)2(μ-Cl)]2 and [Rh(cod)(μ-Cl)]2, on the reaction rate, chemoselectivity, stereoselectivity and formation of tetraphenyldisiloxane in Rh-catalyzed asymmetric hydrosilylation of acetophenone as a model reaction have been studied. Mechanistic aspects of formation of silyl enol ether as a side product in the presence of S-containing ligands are presented.

Intramolecular Keto Lactam Condensation: A Convenient and Straightforward Approach to Bicyclic Vinylogous Lactams

Although the aldol condensation is a well‐known reaction, the aza‐type aldol condensation, namely, the intramolecular condensation of common keto lactams leading to bicyclic vinylogous lactams, is a highly demanding transformation, with potential applications in both organic synthesis and medicinal chemistry. The known methods for this type of cyclization require several steps. In this paper, we disclose a straightforward approach that consists of the in‐situ formation of silyl enol ethers with tert‐butyldimethylsilyl trifluoromethanesulfonate (TBDMSOTf), lactam activation with triflic anhydride (Tf2O), and a tandem cyclocondensation reaction. The reaction can be run in a one‐pot manner or in a two‐step fashion, both under mild conditions. The yields for the one‐pot version were 52–80 %. In some cases, the two‐step version gave higher overall yields (44–85 %) than the one‐pot version.

Rhodium-Catalyzed Dehydrogenative Silylation of Acetophenone Derivatives: Formation of Silyl Enol Ethers versus Silyl Ethers.

A series of rhodium-NSiN complexes (NSiN=bis (pyridine-2-yloxy)methylsilyl fac-coordinated) is reported, including the solid-state structures of [Rh(H)(Cl)(NSiN)(PCy3 )] (Cy=cyclohexane) and [Rh(H)(CF3 SO3 )(NSiN)(coe)] (coe=cis-cyclooctene). The [Rh(H)(CF3 SO3 )(NSiN)(coe)]-catalyzed reaction of acetophenone with silanes performed in an open system was studied. Interestingly, in most of the cases the formation of the corresponding silyl enol ether as major reaction product was observed. However, when the catalytic reactions were performed in closed systems, formation of the corresponding silyl ether was favored. Moreover, theoretical calculations on the reaction of [Rh(H)(CF3 SO3 )(NSiN)(coe)] with HSiMe3 and acetophenone showed that formation of the silyl enol ether is kinetically favored, while the silyl ether is the thermodynamic product. The dehydrogenative silylation entails heterolytic cleavage of the Si-H bond by a metal-ligand cooperative mechanism as the rate-determining step. Silyl transfer from a coordinated trimethylsilyltriflate molecule to the acetophenone followed by proton transfer from the activated acetophenone to the hydride ligand results in the formation of H2 and the corresponding silyl enol ether.

Trimethylsilyl Iodide as a Multifunctional Agent in the One-Pot Synthesis of 9-(1H-Indol-3-yl)xanthen-4-(9H)-ones from O-Methyl Protected Salicylaldehydes, Indoles, and β-Dicarbonyl Compounds

Trimethylsilyl iodide (TMSI) is introduced as an efficient reagent for the one-pot synthesis of 9-(1H-indol-3-yl)xanthen-4-(9H)-ones using the reaction of 2-methoxybenzaldehydes (as O-methyl protected salicylaldehydes), indoles, and β-dicarbonyl compounds. In this protocol, a set of TMSI reactions involving silylation, silyl enol ether formation, methyl deprotection, and nucleophilic substitution/cyclization are performed to furnish the target product. The key step in this protocol is the deprotection of the methoxy group by TMSI.

Studies toward the Synthesis of Palhinine Lycopodium Alkaloids: A Morita–Baylis–Hillman/Intramolecular Diels–Alder Approach

A synthetic route to the isotwistane core of palhinine lycopodium alkaloids is described. A Morita-Baylis-Hillman/intramolecular Diels-Alder (IMDA) strategy sets the vicinal all-carbon quaternary centers present in this family of natural products. The regioselectivity of the IMDA reaction is dictated by the conditions employed for silyl enol ether formation, with one set of conditions providing the core of cardionine and alternate conditions generating the desired isotwistane core of isopalhinine.

A novel and versatile method for the enantioselective syntheses of tropane alkaloids

A full account of the novel and flexible approach to hydroxylated 8-azabicyclo[3,2,1]octan-3-ones and 9-azabicyclo[3,3,1] nonan-3-ones is presented. Using keto-lactams as the starting materials, this two-step method consists of silyl enol ether formation with TBDMSOTf, lactam activation with Tf2O/DTBMP, and halide-promoted cyclization. Radical dechlorination of the resulting 1-halotropan-3-ones led to the corresponding hydroxylated tropan-3-ones, which can be hydrogenated to yield 3α,6β-dihydroxytropanes. Starting from optically active keto-lactams, the method has been applied to the enantioselective syntheses of (+)-(1S,3S,5R,6S)-pervilleine C (6), (+)-(1S,3R,5S,6R)-valeroidine (3), (+)-(1S,3S,5R,6S)-dibenzoyloxytropane (8), and (+)-(1S,3S,5R,6S)-merredissine (9).

Aerobic, Transition-Metal-Free, Direct, and Regiospecific Mono-α-arylation of Ketones: Synthesis and Mechanism by DFT Calculations

We disclose a facile, aerobic, transition-metal-free, direct, and regiospecific mono-α-arylation of ketones to yield aryl benzyl and (cyclo)alkyl benzyl ketones with substitution patterns that are currently inaccessible or challenging to prepare using conventional methods. The transformation is operationally simple, scalable, and environmentally friendly. There is no need for pre-functionalization (i.e., α-halogenation or silyl enol ether formation) or the use of specialized arylating agents (i.e., diaryliodonium salts). DFT calculations suggest that the in situ-generated enolate undergoes direct C-C bond formation with the nitroarene followed by regioselective O2-mediated C-H oxidation.

An unusual Me3SiI-promoted [4+2] annulation and reduction: an efficient approach to construct 4H-benzopyrans

Me(3)SiI-promoted reaction of salicylic aldehydes with β-dicarbonyl compounds provided a facile way to construct 4H-benzopyrans in moderate to good yields. This tandem reaction proceeds with high efficiency through nucleophilic addition, silyl enol ether formation, substitution, reduction, and intramolecular nucleophilic cyclization.

ChemInform Abstract: New, Efficient Synthesis of α‐Chloroketones Using SiCl4/Urea—Hydrogen Peroxide or SiCl4/Iodosylbenzene Reagent Systems.

AbstractA new method for the synthesis of α‐chloroketones is presented.

Reductive Conjugate Addition of Haloalkanes to Enones To Form Silyl Enol Ethers

A new method is presented for tandem reductive conjugate addition and silyl enol ether formation from cyclic and acyclic enones and enals in the presence of a Mn reductant, a Ni(terpyridine) catalyst, and a trialkylchlorosilane. The addition of secondary, tertiary, and hindered primary haloalkanes is demonstrated. Preliminary studies on the mechanism show that the intermediacy of L1(Ni)(η(3)-1-triethylsilyloxyalkenyl)X or in-situ-formed RMnX is unlikely.

Catalytic Formation of Silyl Enol Ethers and Its Applications for Aldol-Type Condensation and Aminomethylation Reactions

A new catalytic method for the synthesis of silyl enol ethers has been developed from the coupling reaction of ketones with CH2═CHSiMe3 by using a ruthenium hydride catalyst (PCy3)2(CO)RuHCl. The synthetic utility of silyl enol ethers was demonstrated for both Mukaiyama aldol condensation and aminomethylation reactions in forming β-hydroxyketones and β-aminoketones, respectively.

New, Efficient Synthesis of α-Chloroketones Using SiCl4/Urea–Hydrogen Peroxide or SiCl4/Iodosylbenzene Reagent Systems

Alkyl aryl ketones on treatment with SiCl4/urea–hydrogen peroxide (UHP) or SiCl4/iodosylbenzne reagent systems afforded α-chloroketones in excllent yields, while ketones with higher enol content provide exclusively α,α-dichloroketones under exceedingly mild conditions. The reaction proceeds via the initial formation of silyl enol ethers. A polarized chlorine intermediate that resulted from the coordination of SiCl4 with the in situ formed trichlorosilyl hypochlorite Cl3SiOCl is thought to be the active chlorinating agent.

A Method for the Preparation of Differentiated trans-1,2-Diol Derivatives with Enantio- and Diastereocontrol

We describe a synthetic sequence that allows for the preparation of optically active trans-1,2-diol monosilyl ether derivatives from ketones, providing a new means for retrosynthetic simplification of differentiated diol and polyol targets. The sequence involves silyl enol ether formation, Shi asymmetric epoxidation, and then regio- and stereospecific addition of hydride, methide, or higher alkylide. The tactical combination presented has not been integrated in synthetic problem solving, so far as we are aware, but has promise for broad application.

Thieme Chemistry Journal Awardees - Where are They Now? Synthesis of Diamantane-Derived N-Heterocyclic Carbenes and Applications in Catalysis

Novel diamantyl-substituted imidazolium salts have been synthesized,characterized and, in addition, analyzed by single-crystal structuralanalysis. The corresponding NHCs ( A-IDAdand M-IDAd) have been prepared in solutionand have been characterized by NMR. They exhibit increased stericdemand and increased lipophilicity relative to the well-known IAd.In comparative studies, these NHCs were tested as ligands in palladium-catalyzedSonogashira reactions of primary alkyl halides and, in addition,as catalysts in an organocatalyzed silyl enol ether formation.

Enantioselective Protonation of Silyl Enolates Catalyzed by a Binap-AgF Complex

A catalytic enantioselective protonation of trimethylsilyl enol ethers using AgF·binap under very mild conditions (CH2Cl2-MeOH, -20 °C to 0 °C) is reported. Generally good to excellent yields and ee’s were obtained. This method allows for preparation of enantiomerically enriched α-chiral ketones from racemic ketones by silyl enol ether formation followed by enantioselective protonation.