aza piancatelli

A novel one-pot protocol that enables sequential execution of an aza-Piancatelli rearrangement and a Conia-ene type reaction has been developed under Lewis acid catalysis. Here, a combination of B(C6 F5 )3 and Cu(OTf)2 , triethylamine, and triphenylphosphine yielded a wide range of cis -fused cyclopentenone-pyrrolidine scaffolds in one pot with good yields and diastereoselectivity.

Sulfoximines make up a class of compounds of growing interest for crop science and medicinal chemistry, but methods for directly incorporating them into complex molecular scaffolds are lacking. Here we report a scandium-catalyzed variant of the aza-Piancatelli cyclization that can directly incorporate sulfoximines as nucleophiles rather than the classical aniline substrates. Starting from 2-furylcarbinols and sulfoximines, the reaction provides direct access to 4-sulfoximinocyclopentenones, a new scaffold bearing cyclopentenone and sulfoximine motifs, both of interest for bioactive compounds...

Cascade aza-Piancatelli reaction and [3+3]/[4+2] cycloaddition reactions are carried out using the ideality principles of pot, atom, and step economy (PASE) synthesis. The reaction resulted in generation of octahydro-4H-cyclopenta[b]pyridin-6-one scaffolds. Moreover, octahydro-5,7a-epoxycyclopenta[cd]isoindol-4-one frameworks of gracilamine alkaloid and a novel decahydro-1H-dicyclopenta[cd,hi]isoindol-6-one were also realized in good yields with excellent regio- and diastereo-selectivities.

The asymmetric synthesis of bridged tetrahydrobenzo[ b ]azepine and oxepine derivatives through chiral Brønsted acid catalyzed asymmetric aza-Piancatelli rearrangement/Michael addition sequence has been developed. The reaction proceeds under mild reaction conditions to afford the final bridged cyclic products in good yields with excellent enantio- and diastereoselectivities.

The aza-Piancatelli reaction has been widely used to synthesize donor-acceptor Stenhouse adducts (DASAs), a new class of molecular photoswitches with unique properties. However, the substitution pattern of furan cores has been limited to position 3, as 3,4-disubstituted furans remain unreactive. Herein, we explore the aza-Piancatelli reaction mechanism using density functional theory (DFT) calculations to understand the influence of the different substituents on the reactivity. We found that all the reaction pathways are kinetically accessible, but the driving force of the reaction is lost in disubstituted furans due to the loss of conjugation in the DASA products...

A new strategy for access to spirocyclopentenonyl oxindole frameworks is disclosed. Suitably anchored furfuryl alcohol at C3 of an oxindole was used for the aza-Piancatelli rearrangement, which furnished spirocyclic aminocyclopentenone frameworks with catalytic phosphomolybdic acid. The scope of the transformation was extended to the carbo-Piancatelli rearrangement with various indole derivatives.

A novel aza-Piancatelli rearrangement triggered cascade reaction has been developed by utilizing methyl furylacrylates as a new type of functionalized furanoxonium ion precursor, permitting rapid and flexible construction of diverse cyclopenta[ b ]pyrrolidinone derivatives. The unprecedented and highly efficient bicyclic γ-lactam product formation is originated from an unusual retro -aza-Piancatelli rearrangement of the major cis -fused multifunctionalized cyclopentenone to the minor trans -fused one followed by a lactamization reaction...

Observation of an unexpected, Lewis acid promoted displacement of latent reactive γ-amino group on cyclopentenone presented unparalleled opportunity for enone functionalization and annulations with indole derivatives, which is developed in the current study. Herein, a vast range of C3/ N -indolyl enones and indole alkaloid-like compound were accessed in excellent yields (up to 99%) and selectivity through a one-pot operation. The mechanism most likely involves an unprecedented trait of Piancatelli-type rearrangement where influence of the gem -diaryl group appeared crucial...

The first Lewis acid and chiral Brønsted acid cooperatively catalyzed asymmetric cascade ring opening/aza-Piancatelli rearrangement reaction of furyl-substituted donor-acceptor cyclopropanes is achieved, enabling the construction of functionalized aminocyclopentenones bearing α-quaternary carbon stereocenters in high yields with excellent enantio- and diastereoselectivities under remarkably low catalyst loading of 0.2-1.2 mol %.

A domino approach to bridged cycloocta[ b ]indolone through a cascade of aza-Piancatelli rearrangement/Friedel-Crafts alkylation is developed. This transformation has been realized by reaction of an indole-tethered 2-furylcarbinol and substituted aniline in the presence of a Lewis acid to initiate aza-Piancatelli rearrangement followed by an in situ intramolecular Friedel-Crafts alkylation to access bridged tetracyclic frameworks in one pot.

Herein, we report the preparation of bridged tetrahydrobenzo[ b ]azepines, which was accomplished via an aza-Piancatelli cyclization/Michael addition sequence in a one-pot fashion from readily available precursors. It is noteworthy that a general method to access these scaffolds was hitherto unprecedented. Additionally, the multifaceted aspects of this process have been exemplified through its application to the synthesis of 2-azabicyclo[3.2.1]octanes and bridged tetrahydrobenzo[ b ]oxepines, along with post-derivatizations...

An enantioselective aza-Piancatelli rearrangement has been developed using a chiral Brønsted acid based on pentacarboxycyclopentadiene (PCCP). This reaction provides rapid access to valuable chiral 4-amino-2-cyclopentenone building blocks from readily available starting material and is operationally simple.

For the first time, an efficient one-pot method for the construction of an angularly fused 5-6-5 aza-tricyclic framework has been developed in a highly stereoselective manner. This domino reaction is a novel combination of aza-Piancatelli rearrangement and intramolecular Diels-Alder reaction, which readily furnishes hexahydro-2a,5-epoxy-cyclopenta[ cd]isoindole adducts, bearing six contiguous stereogenic centers in very good yields. The BBr3 -mediated cleavage of the oxa-bridged adduct results in the formation of octahydro-1 H-cyclopenta[ cd]isoindole, an aza-tricyclic BCE core of a gracilamine alkaloid...

A chiral Brønsted acid catalyzed highly enantio- and diastereoselective cascade cyclization has been developed to streamline the synthesis of valuable multifunctionalized enantioenriched cyclopenta[ f]pyrrolo[1,2- d][1,4]diazepinones bearing three contiguous stereocenters in high yields with excellent control of stereochemistry from a wide range of both readily available 2-furylcarbinols and (1 H-pyrrol-1-yl)anilines, which represents the first asymmetric intramolecular conjugate addition of α,β-unsaturated cycloketones with inert N-substituted pyrroles as well as the first enantioselective aza-piancatelli rearrangement/Friedel-Crafts alkylation cascade reaction...

A new and efficient reaction sequence between 2-furylcarbinols, anilines, and α-haloamides has been developed to afford highly functionalized cyclopenta[ b]piperazinones. This transformation was accomplished through an aza-Piancatelli cyclization/azaoxyallyl cation trapping with a complete control of the diastereoselectivity.

A novel method for the construction of 1-azaspirocycles from 5-alkyl-/-arylamine furylcarbinols though intramolecular aza-Piancatelli rearrangement was developed. By using PPh3 /diethyl azodicarboxylate instead of a Lewis acid, 1-azaspirocyclic compounds were obtained in good yields and the reaction temperature was reduced to room temperature. In addition, substrates with groups that are sensitive to high temperatures or Lewis acids are tolerated under these reaction conditions. This is the first method that is applicable not only to 5-(N-arylaminoalkyl)furylcarbinols with better yields but also to 5-(N-alkylaminoalkyl)furylcarbinols...

An efficient organocatalytic enantioselective aza-Piancatelli rearrangement is disclosed. The powerful process provides rapid access to valuable chiral 4-amino-2-cyclopentenone building blocks from readily available 2-furfurylcarbinols with excellent chemo-, enantio-, and diastereoselectivities under mild reaction conditions.

The first catalytic asymmetric Piancatelli reaction is reported. Catalyzed by a chiral Brønsted acid, the rearrangement of a wide range of furylcarbinols with a series of aniline derivatives provides valuable aminocyclopentenones in high yields as well as excellent enantioselectivities and diastereoselectivities. The high value of the aza-Piancatelli rearrangement was demonstrated by the synthesis of a cyclopentane-based hNK1 antagonist analogue.

A method to extend the scope of the aza-Piancatelli reaction between 2-furylcarbinols and anilines is depicted. We found that 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) is the solvent of choice for this transformation, as it outcompetes the usual solvents in terms of rate and yield. Side reactions and other issues raised by the title reaction are prevented, thereby providing an avenue to complex molecules that were previously inaccessible. Lewis acidity studies and computations were carried out to unveil the role of HFIP...

2-Furylcarbinols undergo a smooth aza-Piancatelli rearrangement followed by Friedel-Crafts alkylation with a bifunctional substrate, (1H-pyrrol-1-yl)aniline, in the presence of 10 mol% In(OTf)3 in acetonitrile at room temperature to afford the corresponding hexahydrobenzo[b]cyclopenta[f]pyrrolo[1,2-d][1,4]diazepin-11(4aH)-one scaffolds in good yields. This method offers significant advantages such as high conversions, mild reaction conditions, short reaction times, and high selectivity. The relative stereochemistry of the product was established by nOe studies...