Donor-acceptor Cyclobutanes Research Articles

Recent Advances on High-Order Dipolar Annulations of Donor–Acceptor Cyclopropanes/Cyclobutanes

AbstractThis short review summarizes the recent impressive developments on the high-order dipolar annulations (HODAs) of donor–acceptor cyclopropanes (DACs) and donor–acceptor cyclobutanes (DABs) to afford medium-sized (hetero)cycles.1 Introduction2 (3+m) (m > 3) Annulations of Donor–Acceptor Cyclopropanes2.1 (3+4) Annulations2.2 (3+5) Annulations3 (4+m) (m > 2) Annulations of Donor–Acceptor Cyclobutanes4 Conclusion

Lewis acid-catalyzed [4 + 2] cycloaddition of donor-acceptor cyclobutanes with iminooxindoles: access to spiro[piperidine-3,2'-oxindoles

A new approach is described for the synthesis of spiro[piperidine-3,2'-oxindoles] in 35-82 yields with excellent stereoselectivity via the [4 + 2] cycloaddition reaction of donor-acceptor cyclobutanes with iminooxindoles in the presence of 10-30 mol% Sc(OTf)3 at room temperature. This methodology provides great potential for building spiro-heterocycle compounds from simple building blocks.

Diastereoselective synthesis of tetrahydrobenzo[b]azocines by Lu(OTf)3-catalyzed [4+4] cycloaddition of donor-acceptor cyclobutanes with anthranils.

The construction of N-heterocyclic eight-membered rings remains challenging due to unfavorable transannular strain. Herein, we report a Lu(OTf)3-catalyzed formal [4+4] cycloaddition reaction of cyclobutane 1,1-diesters with anthranils to deliver oxa-bridged eight-membered heterocycles. This methodology provides great potential to build complex azocine compounds from simple building blocks. Based on our preliminary mechanism studies, a probable mechanism for this annulation pathway has been proposed.

Synthesis of Hexahydropyridazines by [4 + 2] Cycloaddition of Donor-Acceptor Cyclobutanes and cis-Diazenes.

The GaCl3-catalyzed [4 + 2] cycloaddition between alkoxy- and aryl-activated donor-acceptor cyclobutane diesters and cis-diazene 1a (4-phenyl-1,2,4-triazoline-3,5-dione, PTAD) is disclosed. The reaction provides hexahydropyridazine derivatives as single diastereomers in good to excellent yields in most cases. The structural assignment of the cycloadduct 3b was unambiguously established by single-crystal X-ray diffraction.

Lewis acid-catalyzed cyclodimerization of 1-substituted-3-arylvinylindoles leading to highly functionalized fused cyclopenta[b]indoles

An unexpected Lewis acid-catalyzed [3+2] cycloaddition reaction of 1-substituted-3-arylvinylindoles was revealed when we studied the chemistry of donor-acceptor cyclobutanes and 1-substituted-3-arylvinylindoles. This method provides a simple, efficient route to synthesis of highly functionalized fused cyclopenta[b]indoles in good to excellent yields with high diastereoselectivity under mild reaction conditions.

Synthesis of Functionalized Tetrahydropyridines by SnCl4 -Mediated [4+2] Cycloaddition between Donor-Acceptor Cyclobutanes and Nitriles.

Cycloadditions of strained carbocycles promoted by Lewis acids are powerful methods to construct heterocyclic frameworks. In fact, the formal [3+2] cycloadditions of donor-acceptor (DA) cyclopropanes with nitriles has seen particular success in synthesis. In this work, we report on the first [4+2] cycloaddition of nitriles with DA cyclobutanes by Lewis acid activation. Tetrahydropyridine derivatives were obtained in up to 91 % yield from various aryl-activated cyclobutane diesters and aliphatic or aromatic nitriles.

Ring-Opening Reactions of Donor-Acceptor Cyclobutanes with Electron-Rich Arenes, Thiols, and Selenols.

Donor-acceptor (D-A) cyclobutanes with two geminal ester groups as acceptors are reacted with electron-rich arenes as nucleophiles to afford ring-opened products. AlCl3 mediates this Friedel-Crafts-type reaction. A variety of donors and electron-rich arenes are used. Nucleophilic thiols and selenols also trigger this ring-opening reaction. Furthermore, a comparison of various physical parameters has been carried out for several D-A cyclobutanes.

Enantioselective Total Synthesis of (-)-Δ9-Tetrahydrocannabinol via N-Heterocyclic Carbene Catalysis.

Enantioselective syntheses of (-)-Δ8-tetrahydrocannabinol ((-)-Δ8-THC) and (-)-Δ9-THC have been achieved in eight and 10 steps, respectively, from a known cinnamic acid. The syntheses take advantage of an enantioselective N-heterocyclic carbene (NHC)-catalyzed (4 + 2) annulation between donor-acceptor cyclobutanes and cinnamoyl fluorides to construct the highly enantioenriched cycloxyl β-lactone shown. Having constructed this A-ring precursor, elaboration to (-)-Δ8-THC is achieved through β-lactone alcoholysis followed by oxidation, dual decarboxylation, trimethylation, and cationic cyclization. Finally, the conversion to (-)-Δ9-THC is achieved with established chemistry.

Synergetic Tandem Enantiomeric Enrichment in Catalytic Asymmetric Multi-Component Reactions (AMCRs): Highly Enantioselective Construction of Tetracyclic Indolines with Four Continuous Stereocenters

Tetracyclic indolines are ubiquitous skeletons in bioactive natural products and pharmaceuticals, and efficient methods for their enantioselective synthesis are highly desired. Here, we report an efficient three-component formal [2 + 2 + 2] cycloaddition reaction between indoles, 2,3-dihydropyran, and methylene malonates for rapid construction of optically active tetracyclic indolines bearing four continuous stereocenters. Although the optimal catalyst Cu(II)/BOX displays only moderate enantioselectivities in either formal cyclobutanation or [4 + 2] cycloaddition reaction with donor–acceptor cyclobutanes bearing a nonracemizable stereocenter, the collaborative tandem enantiomeric enrichment in the one-pot asymmetric multicomponent reaction is highly effective, thereby affording a wide range of tetracyclic indoline derivatives with excellent diastereo- and enantioselectivities in high yields.

A comparison of the benzylic and the allylic group as a donor in the formal [4+2] cycloaddition to tetrahydropyrans using donor-acceptor cyclobutanes

The allyl group was shown to be preferred over the benzyl group as a donor in the formal [4+2]-cycloaddition reaction between a donor-acceptor cyclobutane and various aldehydes to give tetrahydropyrans.

Reaction of Donor-Acceptor Cyclobutanes with Indoles: A General Protocol for the Formal Total Synthesis of (±)-Strychnine and the Total Synthesis of (±)-Akuammicine.

A ligand-promoted catalytic [4+2] annulation reaction using indole derivatives and donor-acceptor (D-A) cyclobutanes is reported, thus providing an efficient and atom-economical access to versatile cyclohexa-fused indolines with excellent levels of diastereoselectivity and a broad substrate scope. In the presence of a chiral SaBOX ligand, excellent enantioselectivity was realized with up to 94 % ee. This novel synthetic method is applied as a general protocol for the total synthesis of (±)-akuammicine and the formal total synthesis of (±)-strychnine from the same common-core scaffold.

Annulation of Donor–Acceptor Cyclobutanes with N-Heterocyclic Carbenes

Annulation of Donor–Acceptor Cyclobutanes with N-Heterocyclic Carbenes

Enantioselective (4+2) Annulation of Donor–Acceptor Cyclobutanes by N‐Heterocyclic Carbene Catalysis

AbstractHerein we report the enantioselective (4+2) annulation of donor–acceptor cyclobutanes and unsaturated acyl fluorides using N‐heterocyclic carbene catalysis. The reaction allows a 3‐step synthesis of cyclohexyl β‐lactones (25 examples) in excellent chemical yield (most ≥90 %) and stereochemical integrity (all >20:1 d.r., most ≥97:3 e.r.). Mechanistic studies support ester enolate Claisen rearrangement, while derivatizations provide functionalized cyclohexenes and dihydroquinolinones.

Enantioselective (4+2) Annulation of Donor–Acceptor Cyclobutanes by N‐Heterocyclic Carbene Catalysis

Herein we report the enantioselective (4+2) annulation of donor-acceptor cyclobutanes and unsaturated acyl fluorides using N-heterocyclic carbene catalysis. The reaction allows a 3-step synthesis of cyclohexyl β-lactones (25 examples) in excellent chemical yield (most ≥90 %) and stereochemical integrity (all >20:1 d.r., most ≥97:3 e.r.). Mechanistic studies support ester enolate Claisen rearrangement, while derivatizations provide functionalized cyclohexenes and dihydroquinolinones.

ChemInform Abstract: Synthesis of Multisubstituted Silyloxy‐Based Donor—Acceptor Cyclobutanes by an Acid‐Catalyzed [2 + 2] Cycloaddition

AbstractReview: [33 refs.

ChemInform Abstract: Synthetic Applications and Methodological Developments of Donor—Acceptor Cyclopropanes and Related Compounds

AbstractReview: [55 refs.

Synthetic Applications and Methodological Developments of Donor-Acceptor Cyclopropanes and Related Compounds.

Donor-acceptor cyclopropanes are convenient precursors to reactive and versatile 1,3-dipoles, and have found application in the synthesis of a variety of carbo- and heterocyclic scaffolds. This perspective review details our laboratory's use of donor-acceptor cyclopropanes as intermediates toward the total synthesis of various natural products. We also discuss our work in the development of novel cycloadditions and rearrangements of donor-acceptor cyclopropanes and aziridines, as well as an example of an aryne insertion proceeding via fragmentation of a transient donor-acceptor cyclobutane.

Synthesis and reactivity of alkoxy-activated cyclobutane-1,1-dicarboxylates

Donor–acceptor (DA) cyclopropanes are extensively studied and well established as building blocks for the synthesis of highly substituted carbo- and heterocyclic compounds. Despite of similar ring strain, the homologous DA cyclobutanes were long ignored. This personal account details our group's research towards the application of DA cyclobutanes in cycloaddition chemistry.

ChemInform Abstract: Highly Diastereoselective and Enantioselective Formal [4 + 3] Cycloaddition of Donor—Acceptor Cyclobutanes with Nitrones.

AbstractA wide range of multifunctionalized optically active 1,2‐oxazepanes is efficiently obtained by the title reaction using a sterically hindered chiral SaBOX/Cu(II) complex as catalyst.

Synthesis of Tetrahydro‐1,2‐oxazines and Pyrrolidines via Cycloadditions of Donor–Acceptor Cyclobutanes and Nitrosoarenes

AbstractDuring efforts to expand the scope of Lewis‐acid‐catalyzed [4+2] cycloaddition between donor–acceptor cyclobutanes and nitrosoarenes, an unexpected formation of pyrrolidine products was discovered when 50 mol‐% of MgI2 was used as a Lewis acid. It was also observed that the electronics of the nitrosoarene and judicious selection of the Lewis acid catalyst have a profound effect on the regioselectivity of the reaction.