TMS Enol Ethers Research Articles

Synthesis of β-nitro ketones from geminal bromonitroalkanes and silyl enol ethers by visible light photoredox catalysis.

Various β-nitro ketones, including those bearing a β-tertiary carbon, were prepared from geminal bromonitroalkanes and trimethylsilyl enol ethers of a broad range of ketones by visible light photoredox catalysis, which were then easily converted into β-amino ketones, 1,3-amino alcohols, α,β-unsaturated ketones, β-cyano ketones and γ-nitro ketones.

Construction of 8-Azabicyclo[3.2.1]octanes via Sequential DDQ-Mediated Oxidative Mannich Reactions of N-Aryl Pyrrolidines.

A concise synthesis of 8-azabicyclo[3.2.1]octanes via sequential oxidative Mannich reactions is described. This approach involves an intermolecular oxidative Mannich coupling reaction between N-aryl pyrrolidines with TMS enol ether and a subsequent intramolecular oxidative Mannich cyclization of the corresponding silyl enol ether. DDQ is used as a key oxidant for both reactions.

Enantioselective N-Heterocyclic Carbene Catalyzed Synthesis of Functionalized Indenes

An enantioselective NHC (N-heterocyclic carbene) catalyzed synthesis of indenes from bifunctional α,β-unsaturated acyl fluorides and TMS enol ethers has been discovered. The reaction has broad generality (31 examples) and proceeds with high levels of enantioselectivity (most >92:8 er). Mechanistically the reaction likely occurs via a Michael/β-lactonization/decarboxylation sequence. Derivatization studies and limitations are discussed.

N-Heterocyclic Carbene-Catalyzed Generation of α,β-Unsaturated Acyl Imidazoliums: Synthesis of Dihydropyranones by their Reaction with Enolates

Catalytic generation of alpha,beta-unsaturated acyl imidazolium cations and enolates has been achieved, and their involvement in a Michael addition acylation sequence exploited, to provide a range of dihydropyranones. alpha,beta-Unsaturated enol esters, or alpha,beta-unsaturated acid fluorides in association with TMS enol ethers, serve as appropriate substrates for this reaction. The transformation can also be achieved enantioselectively using catalysts derived from chiral triazolium salts.

Total syntheses and structural revision of alpha- and beta-diversonolic esters and total syntheses of diversonol and blennolide C.

Total syntheses and structural revision of alpha- and beta-diversonolic esters and total syntheses of diversonol and blennolide C.

New Domino Silyl Enol Ether Reactions in the Synthesis of a Tetrodecamycin Fragment

AbstractOn heating in toluene at 180 °C for four days the TMS enol ether 7 underwent a domino acid catalysed rearrangement, Diels–Alder cycloaddition and further rearrangement to give the bicyclic TMS enol ether 17, which was converted into a tetrodecamycin precursor 3 in three synthetic steps. Further, monocyclic silyl enol ethers were consecutively treated with mCPBA and bromine to give syn α‐hydroxy α′‐bromo ketones in a one‐pot reaction sequence. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Deracemization of Thiol Esters of α‐Arylpropionic Acids.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Deracemization of thiol esters of α-arylpropionic acids

Racemic thiol esters of α-arylpropionic acids were deracemized by a procedure which featured deprotonation with LDA or KHMDS, transformation into the TMS or TBDMS enol ethers, and enantioselective protonation of the silyl enol ethers using ( R)-1,1′-bi-2-naphthol/SnCl 4. Oxidative hydrolysis of the enantiomerically enriched mixtures of thiol esters thus obtained yielded the ( S)-enantiomers of ibuprofen and naproxen with ees up to 82%.

Total Synthesis of (‐)‐Bafilomycin A1.

A highly stereoselective total synthesis of (-)-bafilomycin A(1), the naturally occurring enantiomer of this potent vacuolar ATPase inhibitor, is described. The synthesis features the highly stereoselective aldol reaction of methyl ketone 8b and aldehyde 60c and a Suzuki cross-coupling reaction of the highly functionalized advanced intermediates 12 and 39. Vinyl iodide 12 was synthesized by a 14-step sequence starting from the readily available beta-alkoxy aldehyde 14, while the vinylboronic acid component 39 was synthesized by a nine-step sequence from beta-hydroxy-alpha-methyl butyrate 44 via a sequence involving the alpha-methoxypropargylation of chiral aldehyde 49 with the alpha-methoxypropargylstannane reagent 54. Syntheses of fragments 12 and 39 also feature diastereoselective double asymmetric crotylboration reactions to set several of the critical stereocenters. The Suzuki cross-coupling of 12 and 39 provided seco ester 40, which following conversion to the seco acid underwent smooth macrolactonization to give 41. The success of the macrocyclization required that C(7)-OH be unprotected. The Mukaiyama aldol reaction between aldehyde 60c and the TMS enol ether generated from 8b provided aldol 65 with high diastereoselectivity. Finally, all silicon protecting groups were removed by treatment of the penultimate intermediate 65 with TAS-F (tris(dimethylamino)sulfonium difluorotrimethylsilicate), thereby completing the total synthesis of (-)-bafilomycin A(1).

Total synthesis of (-)-bafilomycin A(1).

A highly stereoselective total synthesis of (-)-bafilomycin A(1), the naturally occurring enantiomer of this potent vacuolar ATPase inhibitor, is described. The synthesis features the highly stereoselective aldol reaction of methyl ketone 8b and aldehyde 60c and a Suzuki cross-coupling reaction of the highly functionalized advanced intermediates 12 and 39. Vinyl iodide 12 was synthesized by a 14-step sequence starting from the readily available beta-alkoxy aldehyde 14, while the vinylboronic acid component 39 was synthesized by a nine-step sequence from beta-hydroxy-alpha-methyl butyrate 44 via a sequence involving the alpha-methoxypropargylation of chiral aldehyde 49 with the alpha-methoxypropargylstannane reagent 54. Syntheses of fragments 12 and 39 also feature diastereoselective double asymmetric crotylboration reactions to set several of the critical stereocenters. The Suzuki cross-coupling of 12 and 39 provided seco ester 40, which following conversion to the seco acid underwent smooth macrolactonization to give 41. The success of the macrocyclization required that C(7)-OH be unprotected. The Mukaiyama aldol reaction between aldehyde 60c and the TMS enol ether generated from 8b provided aldol 65 with high diastereoselectivity. Finally, all silicon protecting groups were removed by treatment of the penultimate intermediate 65 with TAS-F (tris(dimethylamino)sulfonium difluorotrimethylsilicate), thereby completing the total synthesis of (-)-bafilomycin A(1).

Enantio- and Diastereoselective Synthesis of (Protected) 2-Formyl- and 2-(Hydroxymethyl)-1-phenylalkane-1,3-diols from Chiral 2-Methoxy-3-tosyl-1,3-oxazolidines by Subsequent Asymmetric Formylation and Aldolization

Trimethylsilyl enol ethers are successively converted into chirally protected α-formyl ketones by asymmetric formylation with the 2-methoxy-1,3-oxazolidine 2, transformed into the corresponding, thermodynamically determined (Z)-TMS enol ethers, and then are allowed to condense with aldehydes. All steps proceed with high stereoselectivity. Some synthetic options, arising from the three differentiated oxygen functionalities in the intermediates 8 are illustrated for the title target compounds.

Reaction of Silyl Enol Ethers with Xenon Difluoride in MeCN: Evidence for a Nonclassical Radical Cation Intermediate

The reactions of xenon difluoride in MeCN solution in Pyrex flasks with a series of TMS enol ethers have been investigated. The types of products formed are dependent on the structures of individual enol ethers, but under these conditions all products are consistent with a mechanism involving single electron transfer to un-ionized XeF2 giving a radical cation and subsequent formation of an α-fluoroketone, together with some ketone formation. The results suggest that if the radical cation is particularly stable, fluorodesilylation leads to radical formation, and solvent-derived products are then observed. Using other solvents, such as CFCl3 and C6F6, much more complex mixtures of products are obtained, and this is attributed to a different mode of reaction of xenon difluoride involving ionization to FXe+.

Applications of the β-Azidonation Reaction to Organic Synthesis. α,β-Enones, Conjugate Addition, and γ-Lactam Annulation

The s-azido functionalization reaction provides a mechanistically different enone synthesis that involves treatment of 2 with fluoride anion to effect desilylation and concomitant s-elimination to give 3. Table 1 lists a number of examples of the direct conversion of a TIPS enol ether into the corresponding a,s-enone via a s-azido TIPS enol ether. The s-azido group can be ionized with Me3Al or Me2AlCl and the intermediate enonium ion trapped by a variety of nucleophiles such as an allylstannane, electron-rich aromatics, TMS enol ethers, Et2AlCN, Me2AlCCR, Me4AlLi, and vinylaluminum reagents to give the products listed in Table 2. The diastereoselectivity of the reaction of a 4-substituted enonium ion with indole shows an unusual increase of selectivity with increasing temperature. Reduction of the azide 2 provides access to s-amino TIPS enol ethers 5, which, for example, can be converted into a cinnamide derivative and cyclized via a putative “ene” process into a ?-lactam.

Asymmetric aldol additions catalyzed by chiral phosphoramides: Electronic effects of the aldehyde component

The trichlorosilyl enolates of cyclopentanone and cycloheptanone were prepared by a mercury(II)-catalyzed metathesis from their TMS enol ethers in good yield. These enolates undergo spontaneous addition to aldehydes to provide the aldol adducts syn- 4, 5a-e in high yield and selectivity (dr 19 1 to > 49 1 ). More electron rich aldehydes tend to be more diastereoselective. The reaction of these enolates with aldehydes is also catalyzed by the chiral phosphoramide (S,S)- 1 to provide anti- 4, 5a-e in good to excellent diastereo- (dr 15 1 to 35 1 ) and enantioselectivity (er 84.4 15.6 to 95.9 4.1 ). In these cases, a trend is apparent only with sterically similar benzaldehyde derivatives. In addition, optimization studies suggest that two mechanistically distinct pathways may be operating in the catalyzed reaction.

Iodotrimethylsilane-promoted additions of monoorganocopper compounds to .alpha.,.beta.-unsaturated ketones, esters, and lactones

Conjugate additions with the efficient monoorganocopper-iodotrimethylsilane combination, exemplified mainly with methylcopper, butylcopper, and tert-butylcopper, proceed cleanly, smoothly, and rapidly to a variety of α,β-unsaturated carbonyl compounds; cyclic and acyclic enones, β-alkoxy enones, enoates and lactones in ether, THF, and dichloromethane, often at -78 o C. The RCu-(LiI)-TMSI reagent gives a good economy of group transfer with good to excellent yields of conjugate adducts. Lithium iodide, present from preparation of the organocopper compounds, increases the rate of the reactions and is a favorable component. Additions are faster, but somewhat less selective, in THF than in ether. Careful workup after addition of triethylamine or pyridine at low temperature permits isolation of TMS enol ethers and TMS ketene acetals. Acyclic enones preferentially give the Z-silyl enol ethers. The RCu(LiI)-TMSI system is a most useful alternative to the conventional lithium diorganocuprates in conjugate additions

Branching of Ketosugars by Ethyl Trimethylsilyl-Acetate/Tetra-n-Butylammonium Fluoride

Abstract Hexopyranose- and hexofuranose-uloses, on treatment with ethyl trirnethylsilylacetate/tetra-n-butylammohium fluoride, form β-hydroxy esters or derivatives thereof instead of their TMS-enol ethers. 29Si NMR studies confirm the proposed mechanism.

Synthetic Utility of (Propargyl)dicobalt Hexacarbonyl Cations. A New Cyclopentenone Annelation

AbstractThe regiospecific alkylation of cyclic ketones and TMS enol ethers by the cobalt‐stabilized propargyl cations 1 followed by demetalation and regiospecific acetylene hydration proceeds in good overall yield to produce 1,4‐diketones. The latter are efficiently cyclized in the presence of base to annelated cyclopentenones.

Nouvelles methodes de deshalogenation et de formation d'ethers d'enol trimethylsilyques par action de [formula omitted]Pr 2NLi sur quelques α-bromocetones.

i Pr 2NLi reacts with substituted α-bromoketones to yield the debrominated ketone after hydrolysis or the TMS-enol ether after addition of SiMe 3Cl. Both reactions are quantitative within a few minutes.

An Efficient Synthesis of Dihydrojasmone Utilizing a Cationic [(Propargyl)dicobalt Hexacarbonyl] Complex

Abstract As part of a program to explore the organic chemistry of cobalt-stabilized propargyl cations 1, we recently found that these complexes readily and selectively α-alkylate ketones and ketone derivatives including TMS enol ethers and enol acetates2 (eq. 1).