Cycloisomerization Process Research Articles

ChemInform Abstract: One‐Pot Novel Regioselective Cycloisomerization Synthesis of 2‐Substituted or 3‐Substituted 4H‐Furo[3,2‐c]chromene Through the Intermediate Cyclopropenes of 3‐Diazochroman‐4‐one and Phenylacetylene.

A new class of cyclopropenes containing a chroman-4-one motif were synthesized using 3-diazochroman-4-one and phenylacetylene with rhodium(II) catalyst and followed by cycloisomerization to give 2-substituted or 3-substituted 4H-furo[3,2-c]chromene, respectively. Using BF3·Et2O as catalyst, 2-substituted 4H-furo[3,2-c]chromene was exclusively obtained in 70% yield. Using Cu(OTf)2 as catalyst, 3-substituted 4H-furo[3,2-c]chromene was obtained in 95% yield with 98:2 regioselectivity. A one-pot cascade addition–cycloisomerization process was also developed with no need to isolate cyclopropenes of chroman-4-one intermediates.

ChemInform Abstract: Novel [4 + 2]‐Benzannulation to Access Substituted Benzenes and Polycyclic Aromatic and Benzene‐Fused Heteroaromatic Compounds.

A common [4 + 2]-benzannulation of Morita–Baylis–Hillman acetates of acetylenic aldehydes with boronic acids has been developed for the synthesis of aromatic and heteroaromatic compounds through tandem allylic substitution/hydroarylative cycloisomerization process. This method provides a facile and general route to substituted benzenes, naphthalenes, other polycyclic aromatics, and various benzene-fused heteroaromatic compounds such as benzofuran, benzothiophene, indole, and carbazoles.

ChemInform Abstract: Double Transfer of Chirality in Organocopper‐Mediated Bis(alkylating) Cycloisomerization of Enediynes.

AbstractThe synthesis of chiral benzofulvenes, triggered by organocopper reagents, is achieved through a highly chemo‐, regio‐, diastereo‐, and enantioselective bis(alkylating) cycloisomerization process.

Combinatorial synthesis of nicotine analogs using an Ugi 4-CR/cyclization-reduction strategy.

A practical one-pot synthesis of nicotine analogs from Ugi 4-CR/propargyl adducts is reported. This methodology allows the rapid construction of the pyrrolidine moiety present in nicotine through an intramolecular base-promoted 5-endo cycloisomerization process, followed by a reduction of the resulting mixture of 2- and 3-pyrrolines to afford nicotine analogs in good overall yields.

Novel [4 + 2]-benzannulation to access substituted benzenes and polycyclic aromatic and benzene-fused heteroaromatic compounds.

A common [4 + 2]-benzannulation of Morita-Baylis-Hillman acetates of acetylenic aldehydes with boronic acids has been developed for the synthesis of aromatic and heteroaromatic compounds through tandem allylic substitution/hydroarylative cycloisomerization process. This method provides a facile and general route to substituted benzenes, naphthalenes, other polycyclic aromatics, and various benzene-fused heteroaromatic compounds such as benzofuran, benzothiophene, indole, and carbazoles.

ChemInform Abstract: Iminophosphorane—Phosphines: Versatile Ligands for Homogeneous Catalysis

AbstractReview: [65 refs.

Double Transfer of Chirality in Organocopper‐Mediated bis(Alkylating) Cycloisomerization of Enediynes

AbstractAn original synthesis of chiral benzofulvenes triggered by organocopper reagents is reported. These enantiopure products are available through a highly chemo‐, regio‐, diastereo‐, and enantioselective bis(alkylating) cycloisomerization process. A double chirality transfer (central‐to‐axial‐to‐central) is observed.

Double Transfer of Chirality in Organocopper‐Mediated bis(Alkylating) Cycloisomerization of Enediynes

An original synthesis of chiral benzofulvenes triggered by organocopper reagents is reported. These enantiopure products are available through a highly chemo-, regio-, diastereo-, and enantioselective bis(alkylating) cycloisomerization process. A double chirality transfer (central-to-axial-to-central) is observed.

Iminophosphorane–phosphines: Versatile ligands for homogeneous catalysis

Iminophosphoranes R3PNR are nitrogen analogues of phosphorus ylides that can coordinate transition metals using the lone pair on the nitrogen atom. The integration of supplementary donor sites into the iminophosphorane backbone yields polydentate ligands of increasing interest in both coordination chemistry and catalysis. Herein, a comprehensive account of the applications of mixed ligands featuring both a phosphine and an iminophosphorane moiety in homogeneous catalysis is presented. Among others, metal-catalyzed hydrogenation and transfer hydrogenation reactions, C–C cross-couplings, olefin oligomerization and cyclopropanation processes, allylic alkylation and oxidation reactions, Meyer–Schuster rearrangements and cycloisomerization processes are discussed.

Platinum(II) Catalyzed Enantioselective Cycloisomerizations of 3‐Hydroxylated 1,5‐Enynes

AbstractThe enantioselective cycloisomerization of 3‐hydroxylated 1,5‐enynes into bicyclo[3.1.0]hexanones was investigated by using cyclometalated NHC‐platinum phosphoramidite complexes as pre‐catalysts. Several new complexes were prepared. They generate cationic, electrophilic PtII species that efficiently promote the cycloisomerization process. Enantiomeric excesses up to 81 % were obtained in the reactions of enynes with aryl‐substituted alkyne functions (8 examples, 70–81 % ee).

Synthesis of decahydropyrrolo[2,1,5-cd]indolizine derivatives through RuCl3/AgOTf induced alkene–alkene and alkene–arene double cycloisomerizations

In the presence of RuCl3/AgOTf, pyrrolizidine derivative with styrenyl substituents at the 3,5-positions undergo a 6-exo-trig cyclization and subsequent intramolecular Friedel–Crafts reactions to form decahydropyrrolo[2,1,5-cd]indolizine or decahydrocycl[3.2.2]azine derivatives. The cycloisomerization is highly stereoselective. Presence of electron donating groups on the styrenyl substituents inhibits the double cycloisomerization process and results in a trans to cis epimerization instead. No reaction takes place when electron withdrawing groups are present on the styrenyl substituents. Possible mechanisms are proposed for the observed reactions.

Generation of α,β-Unsaturated Platinum Carbenes from Homopropargylic Alcohols: Rearrangements to Polysubstituted Furans

A number of diversely substituted furans are synthesized via a cycloisomerization process that goes through a unique metal carbene species. Both ligand structure and the nature of the leaving group are evaluated. The characteristics of the carbene intermediate can be modulated, resulting in highly selective hydrogen or silicon group migrations.

ChemInform Abstract: One‐Pot Highly Efficient Synthesis of Substituted Pyrroles and N‐Bridgehead Pyrroles by Zinc‐Catalyzed Multicomponent Reaction.

AbstractA convenient zinc(II) chloride‐catalyzed regioselective propargylation—amination—cycloisomerization process is developed for the synthesis of substituted pyrrole derivatives from propargylic acetates, enoxysilanes and primary amines.

Mechanistic Insights into Nickel-Catalyzed Cycloisomerizations

A nickel-catalyzed cycloisomerization coupling an allylic alcohol with an alkyne has been developed. Mechanistic insights gained through deuterium-labeling crossover studies and stereochemical probes illustrate that oxidation of the allylic alcohol to a metal-free enone is not involved in the cyclization pathway. The intermediacy of a metallacycle directly derived from oxidative cyclization of Ni(0) with the allylic alcohol and alkyne is consistent with the results obtained. The simple mechanistic probes employed could be useful in the study of many classes of cycloisomerization processes.

Hydroalkylation of Alkynyl Ethers via a Gold(I)-Catalyzed 1,5-Hydride Shift/Cyclization Sequence

A series of alkynyl ethers react with an electrophilic gold(I) catalyst to produce a range of structurally complex spiro or fused dihydrofurans and dihydropyrans via a 1,5-hydride shift/cyclization sequence. This hydroalkylation process, which is performed under practical experimental conditions, can be applied to terminal as well as ester-substituted alkynes. It allows the efficient conversion of secondary or tertiary sp(3) C-H bonds into new C-C bonds by the nucleophilic addition of a vinylgold species onto an oxonium intermediate. The stereoselectivity of the cycloisomerization process toward the formation of a new five- or six-membered cycle appears to be dependent on steric factors and the alkyne substitution pattern.

Remarkable anion effects uncovered in the development of a Au(iii)-catalyzed tandem nucleophilic substitution–1,5-enyne cycloisomerization process

(I(t)Pe)AuBr(2)(N-imidate) complexes, prepared in high yield by oxidative bromination, are active catalysts for 1,5-enyne cycloisomerization. An efficient tandem nucleophilic substitution-1,5-enyne cycloisomerization is promoted by these novel Au(III) precatalysts. Catalyst efficacy is affected by the imidate ligand and the silver salt used (e.g. Ag[Al(OC(CF(3))(3))(4)]).

Asymmetric Au(i)-catalyzed synthesis of bicyclo[4.1.0]heptene derivatives via a cycloisomerization process of 1,6-enynes

The enantioselective asymmetric gold-catalyzed cycloisomerization reactions of heteroatom tethered 1,6-enynes are conducted in the presence of a chiral cationic Au(i) catalyst ((R)-4-MeO-3,5-(t-Bu)(2)-MeOBIPHEP-(AuCl)(2)/AgOTf system) in toluene under mild conditions and lead to functionalized bicyclo[4.1.0]heptene derivatives in excellent enantiomeric excesses ranging from 90-98%.

Intramolecular homolytic substitution at the sulfur atom: an alternative way to generate phosphorus- and sulfur-centered radicals

Two efficient procedures involving tin hydride or thiophenol-mediated intramolecular homolytic substitution at the sulfur atom are reported. They lead to the generation of varied P(V)-centered radicals from the corresponding aryl or alkyne thiophosphorus substrates. The radical formed can be trapped by an olefin via an intermolecular addition, leading to the construction of C–P bonds. Thiophosphination of triple bonds was also achieved using a radical cycloisomerization process. Extension of the methodology to sulfur-containing species was examined.

Lewis Super‐Acid Catalyzed Cyclizations: A New Route to Fragrance Compounds

This review deals with the application of Lewis super acids such as Al(III), In(III), and Sn(IV) triflates and triflimidates as catalysts in the synthesis of fragrance materials. Novel catalytic reactions involving C-C and C-heteroatom bond-forming reactions, as well as cycloisomerization processes are presented. In particular, Sn(IV) and Al(III) triflates were employed as catalysts in the selective cyclization of unsaturated alcohols to cyclic ethers, as well as in the cyclization of unsaturated carboxylic acids to lactones. The addition of thiols and thioacids to non-activated olefins, both in intra- and intermolecular versions, was efficiently catalyzed by In(III) derivatives. Sn(IV) Triflimidates catalyzed the cycloisomerization of highly substituted 1,6-dienes to gem-dimethyl-substituted cyclohexanes bearing an isopropylidene substituent. The hydroformylation of these unsaturated substrates, catalyzed by a Rh(I) complex with a bulky phosphite ligand, selectively afforded the corresponding linear aldehydes. The olfactory evaluation of selected heterocycles, carbocycles, and aldehydes synthesized is also discussed.

A Rhodium-Catalyzed C−H Activation/Cycloisomerization Tandem

A reaction cascade comprising a rhodium-catalyzed C-H activation, a subsequent hydrometalation of an alkylidene cyclopropane in vicinity, regioselective C-C bond activation of the flanking cyclopropane ring, followed by reductive elimination of the resulting metallacycle, opens a new entry into functionalized cycloheptene derivatives. This crossover of C-H activation and higher order cycloaddition has been performed in two different formats, either using alkylidenecyclopropanes with a lateral vinylpyridine moiety or with a pending aldehyde group as the trigger. The reaction tolerates various functional groups, leaves chiral centers alpha to the reacting sites unaffected, and proceeds with excellent stereoselectivity. Labeling experiments support the proposed mechanism explaining the observed net cycloisomerization process.