Enol Phosphates Research Articles

Palladium on Layered Double Hydroxide: A Heterogeneous System for the Enol Phosphate Carbon-Oxygen Bond Activation in Aqueous Media

In this work, a new catalytic approach for the C-O activation of enol phosphates based on a palladium supported on layered double hydroxide was developed. In this case, two different ketene aminal phosphates were used as models to study the synthesis ofα-phenyl enecarbamates N-Boc/CBz under the Suzuki-Miyaura conditions. The use of an ortho-bromoaniline as precursor allowed the synthesis of the 2-phenyl indole through an arylation/Heck cyclization. Catalyst reusability enabled the synthesis of the heterocycle in moderate yields for four consecutive runs.

Rapid, Practical and Efficient Synthesis of Enol Phosphates from β-Keto Esters and Phosphites

报道了一种利用 β -酮酯通过Atherton-Todd反应合成烯醇磷酸酯的方法.该反应时间短，底物耐受性良好，产率中等，且条件温和.该合成策略为烯醇磷酸酯的合成提供低成本和实用的方法.

Aluminum Chloride Promoted Cross‐Coupling of Trisubstituted Enol Phosphates with Organozinc Reagents En Route to the Stereoselective Synthesis of Tamoxifen and Its Analogues

A new method for the stereoselective cross‐coupling reaction of arylzinc chlorides with trisubstituted enol phosphates is described. The developed method requires aluminum chloride as a promoter, and the reaction conditions tolerate various functional groups. The observed reactivity pattern of trisubstituted enol phosphates was used for the stereoselective preparation of tamoxifen and its analogues.

ChemInform Abstract: Selective Alkenylation and Hydroalkenylation of Enol Phosphates Through Direct C—H Functionalization.

AbstractThe first Rh‐catalyzed cross‐coupling reactions of enol phosphates with a variety of activated alkenes and propyne derivatives (XIV) are described.

ChemInform Abstract: Activation of Marginally Reactive Boron Enolates by MeLi for the Formation of Enol Phosphates and Synthesis of the Δ9‐THC Intermediate.

The addition of MeLi to boron enolates produced by the 1,4-addition of Ar2Cu(CN)Li2 to BF3·OEt2-activated enones was followed by the reaction with ClP(O)(OEt)2 to afford the corresponding enol phosphates in moderate to good yields. The scope of this method was examined with sterically hindered or electronically biased enones and/or reagents. This activation of boron enolates was successfully applied to the synthesis of the methyl ether of Δ9-tetrahydrocannabinol.

Selective Alkenylation and Hydroalkenylation of Enol Phosphates through Direct CH Functionalization

AbstractAn efficient and selective Rh‐catalyzed direct CH functionalization reaction of enol phosphates was developed. The method is applicable to a variety of coupling partners, including activated alkenes, alkynes, and allenes, and leads to the formation of various valuable alkenylated and hydroalkenylated enol phosphates through the action of the phosphate directing group. The versatility and utility of the coupling products were demonstrated through further transformations into synthetically useful building blocks.

Selective Alkenylation and Hydroalkenylation of Enol Phosphates through Direct C-H Functionalization.

An efficient and selective Rh-catalyzed direct CH functionalization reaction of enol phosphates was developed. The method is applicable to a variety of coupling partners, including activated alkenes, alkynes, and allenes, and leads to the formation of various valuable alkenylated and hydroalkenylated enol phosphates through the action of the phosphate directing group. The versatility and utility of the coupling products were demonstrated through further transformations into synthetically useful building blocks.

Activation of Marginally Reactive Boron Enolates by MeLi for the Formation of Enol Phosphates and Synthesis of the Δ(9)-THC Intermediate.

The addition of MeLi to boron enolates produced by the 1,4-addition of Ar2Cu(CN)Li2 to BF3·OEt2-activated enones was followed by the reaction with ClP(O)(OEt)2 to afford the corresponding enol phosphates in moderate to good yields. The scope of this method was examined with sterically hindered or electronically biased enones and/or reagents. This activation of boron enolates was successfully applied to the synthesis of the methyl ether of Δ(9)-tetrahydrocannabinol.

Asymmetric synthesis of 5,7-O-dimethyleucomols via enantioselective oxidation of enol phosphates

The asymmetric synthesis of some derivatives of the homoisoflavone class, (S)-(−)- and (R)-(+)-5,7-O-dimethyleucomols, and (−)-homoisoflavone epoxide, based on the asymmetric oxidation of the corresponding enol phosphates, is described. The influence of electronic and steric effects of the enol phosphate substituents on the facial stereoselectivity of oxidation was observed.

Asymmetric Synthesis of Eucomol via Enantioselective Oxidation of Enol Phosphate

GRAPHICAL ABSTRACT

Annulated N‐Heterocycles by Tandem Gold(I)‐Catalyzed [3,3]‐Rearrangement/Nazarov Reaction of Propargylic Ester Derivatives: an Experimental and Computational Study

AbstractThe gold(I)‐catalyzed tandem rearrangement/Nazarov reaction of propargylic ester derivatives is a useful strategy for the synthesis of cyclopenta‐fused N‐heterocyclic structures present in many natural compounds. Readily available lactams are converted into enol phosphates and triflates and coupled to propargyl alcohols under Sonogashira conditions. After acetylation, the gold‐catalyzed rearrangement of the enynyl acetates readily occurs when using 3–5 mol‐% of a gold(I) catalyst. The rearrangement generates a divinyl cation which undergoes a 4π electrocyclization (Nazarov reaction) leading to the target compound in good to excellent yield. This process has been studied in details both experimentally and computationally to understand the influence of both the reaction conditions and substrate structural features on the reaction rate and regioselectivity, as well as the torquoselectivity in the ring closure step. A series of examples illustrates at the end the scope of the reaction.

Efficient methods for enol phosphate synthesis using carbon-centred magnesium bases.

Efficient conversion of ketones into kinetic enol phosphates under mild and accessible conditions has been realised using the developed methods with di-tert-butylmagnesium and bismesitylmagnesium. Optimisation of the quench protocol resulted in high yields of enol phosphates from a range of cyclohexanones and aryl methyl ketones, with tolerance of a range of additional functional units.

Enol phosphates of phosphorylated derivatives of furylacetic aldehyde and furylpiruvic acid

Phosphorylated derivatives of isomeric furylacetic aldehydes and furylpiruvic acids have been synthesized via formylation and oxalylation of dialkyl (ethoxycarbonylfuryl)methanephosphonates under conditions of the Claisen reaction. 1H, 13C, and 31P NMR spectroscopy studies have shown that the products exist as equilibrium mixtures of the carbonyl compounds and its E- and Z-enol forms in chloroform solutions. Acylation of these substances with diethyl chlorophosphate has yielded the corresponding enol phosphates. Influence of the substituents location in the furan ring on predominance of cis- or trans-configuration has been demonstrated.

ChemInform Abstract: An Approach to a Bislactone Skeleton: A Scalable Total Synthesis of (.+‐.)‐Penifulvin A.

An efficient and scalable total synthesis of the architecturally challenging sesquiterpenoid (±)-penifulvin A has been accomplished via a 12-step sequence with an overall yield of 16%. For the construction of this structurally complex tetracyclic molecule, the key steps used included 1,4-conjugate addition, a Pd(0) catalyzed cross-coupling reaction between an enol phosphate and trimethyl aluminum, Claisen rearrangement using the Johnson orthoester protocol, Ti(III)-mediated reductive epoxide opening–cyclization, Lewis acid catalyzed epoxy-aldehyde rearrangement, and finally a substrate controlled oxidative cascade lactonization process.

Cyclopropane pipecolic acids as templates for linear and cyclic peptidomimetics: application in the synthesis of an Arg-Gly-Asp (RGD)-containing peptide as an αvβ3 integrin ligand.

The synthesis and evaluation of substituted cyclopropane pipecolic acids (CPA) as conformationally restricted templates for linear and cyclic peptidomimetics is reported. A variety of differently substituted (poly)hydroxy- and amino-2-azabicyclo[4.1.0]heptane-1-carboxylic acids were prepared by means of the Pd-catalyzed methoxycarbonylation of suitably functionalized lactam-derived enol phosphates, followed by OH-directed cyclopropanation. CPAs were successfully introduced into a linear peptide sequence to assess the cis/trans isomerism about the pipecolic acid peptide bond, and in a cyclic peptidomimetic that bore the Arg-Gly-Asp (RGD) sequence, which displayed nanomolar activity as antagonist of the αvβ3 integrin in M21 human melanoma cells. Thus, CPAs appear to be suitable for the generation of novel peptidomimetics for drug discovery.

Synthesis of Bis(arylethynyl) Selenides by One‐Pot Protocol

ABSTRACTAn efficient method without using terminal arylacetylenes as substrates for the synthesis of bis(arylethynyl) selenides 1 (ArCCSeCCAr) was described, and a series of compounds 1a−1m have been obtained by a one‐pot three‐step strategy from the corresponding bis(arylethanonyl) selenides. The mechanism was identified through trapping and characterization of a key intermediate 2a, and an elimination using it directly. The results from experiments indicated that the reaction procedure involves the formation of the enol phosphate and a subsequent base‐induced elimination.

A Short, Chemo‐Enzymatic Synthesis of Both Enantiomers of trans‐3‐Hydroxy­pipecolic Acid

AbstractA short synthesis of both enantiomers of trans‐3‐hydroxypipecolic acid was based on the Suzuki–Miyaura reaction of a lactam‐derived enol phosphate and the lipase‐catalyzed kinetic resolution of the alcohol obtained by hydroboration/oxidation of the coupling product. The RuCl3‐catalyzed oxidation of the heteroaryl group introduced by the Suzuki–Miyaura coupling eventually afforded, in six or seven steps, the target compounds in 15–17 % overall yield.

An approach to a bislactone skeleton: a scalable total synthesis of (±)-penifulvin A.

An efficient and scalable total synthesis of the architecturally challenging sesquiterpenoid (±)-penifulvin A has been accomplished via a 12-step sequence with an overall yield of 16%. For the construction of this structurally complex tetracyclic molecule, the key steps used included 1,4-conjugate addition, a Pd(0) catalyzed cross-coupling reaction between an enol phosphate and trimethyl aluminum, Claisen rearrangement using the Johnson orthoester protocol, Ti(III)-mediated reductive epoxide opening-cyclization, Lewis acid catalyzed epoxy-aldehyde rearrangement, and finally a substrate controlled oxidative cascade lactonization process.

Thiamine pyrophosphate stimulates acetone activation by Desulfococcus biacutus as monitored by a fluorogenic ATP analogue.

Acetone can be degraded by aerobic and anaerobic microorganisms. Studies with the strictly anaerobic sulfate-reducing bacterium Desulfococcus biacutus indicate that acetone degradation by these bacteria starts with an ATP-dependent carbonylation reaction leading to acetoacetaldehyde as the first reaction product. The reaction represents the second example of a carbonylation reaction in the biochemistry of strictly anaerobic bacteria, but the exact mechanism and dependence on cofactors are still unclear. Here, we use a novel fluorogenic ATP analogue to investigate its mechanism. We find that thiamine pyrophosphate is a cofactor of this ATP-dependent reaction. The products of ATP cleavage are AMP and pyrophosphate, providing first insights into the reaction mechanism by indicating that the reaction proceeds without intermediate formation of acetone enol phosphate.

ChemInform Abstract: Synthesis of Vinylogous Amides by Gold(I)‐Catalyzed Cyclization of N‐Boc‐Protected 6‐Alkynyl‐3,4‐dihydro‐2H‐pyridines.

The gold(I)-catalyzed cyclization of N-Boc-protected 6-alkynyl-3,4-dihydro-2H-pyridines, prepared by the Sonogashira coupling of lactam-derived enol triflates or phosphates, provides vinylogous amides, which are useful intermediates in the synthesis of natural compounds. The Au(I)-catalyzed reaction is carried out with Ph3PAuOTf as a catalyst and proceeds via a 6-endo-dig cyclization to form a vinylgold species that after protodeauration generates a cyclic carbamate intermediate. This intermediate is in most cases not isolated, but the addition of a base to the reaction mixture rapidly and quantitatively delivers the target vinylogous amide. The first synthesis of a natural compound from Sonneratia hainanensis has been accomplished by this approach.