Regioselective annulation of propargyl alcohols with ambident-enols: A Ca(II)-catalyzed trisubstituted benzochromene synthesis

Highly regioselective, 6-endo cyclization between propargyl alcohols and ambident enols such as naphthols, 4-hydroxy coumarin, cyclohexane-1,3-dione, 5,5-dimethylcyclohexane-1,3-dione is described using Ca(OTf)₂ under solvent free conditions. The reaction proceeds through a cascade annulation which involves an etherification, Claisen type rearrangement, allene formation and endocyclization. Further, we extended this method to the synthesis of iodo-derivative and demonstrated the reactivity in cross-coupling reactions.     

Synthesis of β,γ-disubstituted-γ-lactones through a Johnson–Claisen rearrangement: a short route to xylobovide,nor-canadensolide,canadensolide, sporothriolide and santolinolide

The Johnson–Claisen rearrangement of allyl alcohols with chiral vicinal diol functionality was employed to access chiral β,γ-disubstituted-γ-lactones in high enantio- and diastereoselectivity. These were efficiently converted into nor-canadensolide, the advanced γ-(lactone–lactol) intermediate for xylobovide, canadensolide and sporothriolide and the lactone moiety of the santolinolides.     

A Base-Mediated Alternative to the Orthoester Claisen Rearrangement

The bromo-acetals (2), which may be prepared from allylic alcohols by reaction with 1,2-dibromo-1-ethoxyethane, may be converted in HMPA-Et³N to allyl 1-ethoxyvinyl ethers (1, R⁵ = Et) which undergo Claisen rearrangement.     

Microwave-assisted domino access to C2-chain functionalized furans from tertiary propargyl vinyl ethers

Tertiary propargyl vinyl ethers armed with an electron-withdrawing group (amide or ester) at the tertiary propargylic position have been efficiently transformed into trisubstituted C(2)-chain functionalized furans. The metal-free domino transformation involves a microwave-assisted tandem [3,3]-propargyl Claisen rearrangement/5-exo-dig O-cyclization reaction. The manifold can be performed in a one-pot fashion from the primary components (1,2-ketoester/1,2-ketoamide or tertiary propargyl alcohols).     

The diazo route to diazonamide A: studies on the tyrosine-derived fragment

Various approaches to the tyrosine-derived fragment of the marine secondary metabolite diazonamide A are described. Initial efforts were focused on the originally proposed structure of the natural product, and a feasibility study established that a model 4-aryltryptamine could be readily prepared. Protected 4-bromotryptamine underwent Pd0-catalyzed coupling with the boronic acid derived from 2-bromophenyl allyl ether by Claisen rearrangement, O-methylation and lithiation-boration. The resulting biaryl was elaborated into an alpha-diazo-beta-ketoester, dirhodium(II)-catalyzed reaction of which with N-Z-valinamide gave the desired tryptamine-oxazole following cyclodehydration of the intermediate ketoamide. A potential precursor to the benzofuran ring of the original structure of diazonamide A was prepared in eight steps from N-Z-tyrosine tert-butyl ester. Iodination, O-protection and Stille coupling gave the cinnamyl alcohol 25, converted via the bromide into the allyl aryl ether 27. Subsequent Claisen rearrangement and oxidative cleavage of the alkene gave the lactol 29, converted into the desired benzofuranone 31. The revision in the structure of diazonamide A to 2 resulted in the targeting of an alternative tyrosine-derived model benzofuranone 41 synthesized in four steps from N-Z-tyrosine methyl ester 36 by a route involving Claisen rearrangement of cinnamyl ether 37. Poor yields in this sequence prompted an investigation into the intramolecular Heck reaction as a route to benzofuranone 50. Coupling of 3-iodotyrosine 44 with 2-phenylbutenoic acid 48 gave ester 49 that readily underwent intramolecular Heck reaction to give benzofuranone 50, albeit with poor stereocontrol.     

Transition-metal-mediated cascade reactions: the water-accelerated carboalumination-Claisen rearrangement-carbonyl addition reaction

[Chemical reaction: See text] A three-step cascade reaction involving a water-accelerated catalytic carboalumination, a Claisen rearrangement, and a nucleophilic carbonyl addition converts terminal alkynes and allyl vinyl ethers into allylic alcohols containing up to three contiguous asymmetric carbon centers. Stoichiometric quantities of water as an additive increase the rate of the [3,3] sigmatropic rearrangement as well as the diastereoselectivity of the carbonyl addition process. Reaction products contain 1,6-diene functionalities that are readily cyclized to substituted cyclopentenes. An extension of this methodology to a sequence involving a [1,3] sigmatropic shift was feasible with a cyclopropylmethyl vinyl ether substrate.     

A spin-coupled study of the Claisen rearrangement of allyl vinyl ether

The spin-coupled (SC) form of modern valence bond (VB) theory is utilised to examine the electronic structure of the transition state (TS) and the electronic reaction mechanism of the Claisen rearrangement of allyl vinyl ether. The differences between the spin-coupling patterns and orbital overlap integrals at the optimised TS geometries obtained using B3LYP/6-31G^*, MP2/6-31G^* and MP4(SDQ)/6-31G^* wavefunctions are minimal, and the SC picture suggests that the TS is non-aromatic. SC calculations along the intrinsic reaction coordinates computed at these three levels of theory also produce near identical results. The SC wavefunctions at different stages of the reaction provide easily interpretable orbital diagrams which, in combination with the changes in the orbital overlap integrals, indicate an electronic reaction mechanism involving concerted, though not entirely synchronous, bond breaking and bond formation processes. The evolution of the active space spin-coupling pattern, which is closely related to the classical VB concept of resonance, combined with the changes in the orbital overlap integrals, show that the reaction path involves a region in which the electronic structure of the reacting system becomes similar to that of benzene. This suggests that during the Claisen rearrangement the reacting system can attain moderately aromatic character but that this does not necessarily happen at the TS. The results of the SC analysis indicate that the most appropriate schematic representation of the Claisen rearrangement is furnished by a homolytic mechanism in which six harpoons describe the changes in the bonding pattern from reactant to product     

Synthesis of alkynyl ethers and low-temperature sigmatropic rearrangement of allyl and benzyl alkynyl ethers

Alpha-alkoxy ketones 3 can be transformed into 1-alkynyl ethers 5 by a two-step procedure involving formation of the enol triflate or phosphate and base-induced elimination. Performing the same reaction sequence with allylic alcohols (R2OH, R2 = allyl) furnishes instead gamma,delta-unsaturated carboxylic acid derivatives 6, derived from [3,3]-sigmatropic rearrangement of the intermediate allyl alkynyl ethers at -78 degrees C and trapping of the subsequently formed ketene with nucleophiles (Nu-H). Benzyl alkynyl ether 5 (R2 = benzyl) rearranges to indanone 7 upon heating to 60 degrees C.     

Wolff rearrangement of alpha-diazoketones using in situ generated silver nanoclusters as electron mediators

[reaction: see text] We report Wolff rearrangement of alpha-diazoketones by in situ generated silver nanoclusters (Ag(n)(), 2-4 nm) from silver(I) oxide (Ag(2)O) involving a nonclassical electron-transfer process. Our results show that Ag(n)()(+)/Ag(n)()(0) redox couple allows the initial removal of an electron from alpha-diazoketone and its back-donation after chemical reaction(s). Controlled potential coulometry (CPC) of various alpha-diazoketones results in the realization of Wolff-rearranged carboxylic acids in excellent yields.     

Gold(I)/Chiral N,N′‐Dioxide–Nickel(II) Relay Catalysis for Asymmetric Tandem Intermolecular Hydroalkoxylation/Claisen Rearrangement

A highly efficient asymmetric cascade reaction between alkynyl esters and allylic alcohols has been realized. Key to success was the combination of a hydroalkoxylation reaction catalyzed by a π‐acidic gold(I) complex with a Claisen rearrangement catalyzed by a chiral Lewis acidic N,N′‐dioxide–nickel(II) complex. A range of acyclic α‐allyl β‐keto esters were synthesized in high yields (up to 99 %) with good diastereoselectivities (up to 97:3) and excellent enantioselectivities (up to 99 % ee ) under mild reaction conditions. These products can be easily transformed into optically active β‐hydroxy esters, β‐hydroxy acids, or 1,3‐diols.     

Gold(I)/Chiral N,N′-Dioxide–Nickel(II) Relay Catalysis for Asymmetric Tandem Intermolecular Hydroalkoxylation/Claisen Rearrangement

A highly efficient asymmetric cascade reaction between alkynyl esters and allylic alcohols has been realized. Key to success was the combination of a hydroalkoxylation reaction catalyzed by a π-acidic gold(I) complex with a Claisen rearrangement catalyzed by a chiral Lewis acidic N,N′-dioxide–nickel(II) complex. A range of acyclic α-allyl β-keto esters were synthesized in high yields (up to 99 %) with good diastereoselectivities (up to 97:3) and excellent enantioselectivities (up to 99 % ee) under mild reaction conditions. These products can be easily transformed into optically active β-hydroxy esters, β-hydroxy acids, or 1,3-diols.     

Microwave-assisted Claisen rearrangement of naphthyl 2-propynyl ethers: synthesis of naphthofurans

An efficient two-step approach for the synthesis of naphtho[1,2-b]furans and naphtho[2,1-b]furans has been developed. Various functionalized propargyl alcohols were etherified with α- or β-naphthol under Mitsunobu reaction conditions to give naphthyl 2-propynyl ethers, which underwent a facile microwave-assisted Claisen rearrangement and concomitant anionic cyclization to yield naphthofuran derivatives under basic reaction conditions.     

Cascade‐ and Orthoamide‐Type Overman Rearrangements of Allylic Vicinal Diols

This article describes the details of two new types of Overman rearrangement from allylic vicinal diols. Starting from identical diols, both bis(imidate)s and cyclic orthoamides were selectively synthesized by simply changing the reaction conditions. Whilst exposure of the bis(imidate)s to thermal conditions initiated the double Overman rearrangement to introduce two identical nitrogen groups in a single operation (the cascade‐type Overman rearrangement), the reaction of cyclic orthoamides resulted in a single rearrangement (the orthoamide‐type Overman rearrangement). The newly generated allylic alcohols from the orthoamide‐type reaction can potentially undergo a variety of further transformations. For instance, we demonstrated an Overman/Claisen sequence in one pot. The most conspicuous feature of this method is that it offers precise control over the number of Overman rearrangements from the same allylic vicinal diols. This method also excludes the tedious protecting‐group manipulations of the homoallylic alcohols, which are necessary in conventional Overman rearrangements. All of the performed rearrangements proceeded in a completely diastereoselective fashion through a chair‐like transition state.     

Tandem enyne metathesis and claisen rearrangement: a versatile approach to conjugated dienes of variable substitution patterns

To extend the versatility of the ruthenium carbene-promoted enyne metathesis, it was combined with an Ireland ester enolate Claisen rearrangement. This reaction sequence provided conjugated dienes of higher substitution pattern than that obtained through a cross-enyne metathesis alone. The Ireland-Claisen was conducted across both acyclic and cyclic dienes produced from cross-metathesis and methylene-free enyne metathesis, respectively. In the case of cyclodienes, the Ireland-Claisen rearrangement produced s-trans locked dienes which underwent mode-selective ene reaction. The tandem, sequential use of the Ireland-Claisen rearrangement also proved suitable for chirality transfer originating from chiral propargylic alcohols. Last, the tandem metathesis/Ireland-Claisen was utilized to access 4-substituted-3,5-cyclohexadiene diol derivatives, which are valuable chiral intermediates for natural product synthesis. The combination of this pericyclic reaction with a catalytic metathesis reaction extends the versatility of cross-metathesis since additional diene motifs can be accessed.     

Gold(I)-catalyzed propargyl Claisen rearrangement

Homoallenic alcohols are prepared from propargyl vinyl ethers using a trinuclear gold(I)-oxo complex, [(Ph3PAu)3O]BF4, as a catalyst for propargyl Claisen rearrangement at room temperature. The gold(I)-catalyzed reaction is effective for a diverse collection of propargyl vinyl ethers, including substrates containing aryl and alkyl groups at the propargylic position, and hydrogen, aryl, and alkyl substituents at the alkyne terminus. Tertiary propargyl vinyl ethers can be employed in the reaction, at slightly elevated temperatures, to afford tetrasubstituted allenes. Importantly, the rearrangement of 1,2-disubstituted vinyl ethers proceeds with excellent diastereoselectivity, and the rearrangement of chiral nonracemic propargyl vinyl ethers proceeds with excellent chirality transfer to furnish enantioenriched allenes.     

Stereocontrolled Total Synthesis of (+)-trans-Dihydronarciclasine

A highly stereoselective and efficient total synthesis of trans-dihydronarciclasine from a readily available chiral starting material was developed. The synthesis defines two of the five stereogenic centers of the natural product by an amino acid ester-enolate Claisen rearrangement. The other three stereogenic centers are created in a highly stereocontrolled fashion via a six-ring vinylogous ester intermediate, which is generated from the γ,δ-unsaturated ester functional group of the Claisen rearrangement product in an efficient three-step sequence. This concise total synthesis exemplifies the use of a highly regioselective Friedel-Crafts-type cyclization to form the B ring via an isocyanate intermediate derived from an N-Boc group, which is superior to the conventional method using an imino triflate intermediate. This same N-Boc group is employed to give high selectivity in the Claisen rearrangement earlier in the sequence.     

Ruthenium-catalyzed cyclopropanation of alkenes using propargylic carboxylates as precursors of vinylcarbenoids

Intermolecular cyclopropanation reactions of various alkenes with propargylic carboxylates 1 are catalyzed by [RuCl2(CO)3]2 to give vinylcyclopropanes 2 in good yields. The key intermediate of the reaction is a vinylcarbene complex generated in situ by nucleophilic attack of a carbonyl oxygen of the carboxylates to an internal carbon of the alkyne activated by the ruthenium complex. A variety of transition-metal compounds other than the Ru compound can also be employed in this system. Similar cyclopropanation proceeds with conjugated dienes as well to give trans-vic-divinylcyclopropane derivatives and cycloheptadiene derivatives 5, the latter being thermally derived from the initially formed cis-vic-isomers via Cope-type rearrangement. The present reaction is chemically equivalent to the transition metal-catalyzed cyclopropanation reaction using alpha-diazoketones as carbenoid precursors.     

Claisen ortho ester rearrangement with trimethyl β-(methoxy)orthopropionate: a thermally stable synthon for the preparation of methyl α-substituted acrylates

Trimethyl β-(methoxy)orthopropionate, a compound which is thermally stable at 190 °C for prolonged times, may be utilized as a synthon for the preparation of methyl α-substituted acrylates via Claisen ortho ester rearrangement with allylic alcohols followed by β-elimination of methanol with base.     

Formal synthesis of (-)-perhydrohistrionicotoxin via cyclic amino acid ester-enolate Claisen rearrangement and ring-closing metathesis

[reaction: see text] We have successfully synthesized an advanced synthetic intermediate, hydroxy lactam 3, which has previously been converted to perhydrohistrionicotoxin. An important feature of this synthesis is the creation of stereogenic centers by using the cyclic amino acid ester-enolate Claisen rearrangement together with a ring-closing metathesis for azaspirocyclic skeleton construction.     

Photoinduced one pot transformation of 2-phenyl-4-ethylidene-5(4H)-oxazolone and allylic alcohols to γ, δ-unsaturated N-benzoyl amides

Photolysis of 2-Phenyl-4-ethylidene-5(4H)-oxazolones in the presence of allylic alcohols resulted in a novel one-pot transformation to γ,δ-unsaturated N-benzoyl amides via decarbonylation, nucleophilic addition of allylic alcohols, photoinduced hydrogen transfer and the Claisen rearrangement.