Rh-catalyzed Cycloisomerization Research Articles

A spirosilane ligand induced highly enantioselective Rh-catalyzed cycloisomerization of 1,6-enynes

Transition metal-catalyzed cycloisomerization of 1,6-enynes is a highly effective approach to generating five-membered rings. Among the various catalytic systems developed, the use of chiral ligands in Rh-catalyzed cycloisomerization induced exceptional reactivity and enantioselectivity. In this study, we describe a novel approach to obtained kinds of five-membered rings via Rh-catalyzed cycloisomerization of N-aryl 1,6-enynes, employing a novel spirosilane diphosphine ligand with a significantly enhanced enantioselectivities. Mechanistic experiments and DFT calculations have provided insights into the reaction mechanism.

Theoretical Studies on Rh-Catalyzed Cycloisomerization of Homopropargylallene-Alkynes through C(sp3)–C(sp) Bond Activation

A systematic theoretical study has been carried out with the aid of density functional theory (DFT) calculations on the mechanism of the Rh-catalyzed cycloisomerization of homopropargylallene-alkynes through C(sp3)–C(sp) bond activation. The DFT results indicate that the catalytic cycle is divided into four main processes involving oxidative coupling, insertion, 1,3-alkyl migration, and 1,2-alkyl migration or 1,2-H migration. It is found that a Rh(I) Fischer carbene intermediate, which is derived from the third process 1,3-alkyl migration, selectively determines the formation of the six/five/five tricycle Product 1 or the six/five/four tricycle Product 2, depending on the substitutes on the substrates. The origin of cycloisomerization product selectivity has also been addressed.

A Rh-Catalyzed Cycloisomerization/Diels-Alder Cascade Reaction of 1,5-Bisallenes for the Synthesis of Polycyclic Heterocycles.

A novel methodology to transform bisallenes into a variety of polycyclic derivatives employing rhodium(I) catalysis has been developed. This transformation encompasses an intramolecular Rh-catalyzed cycloisomerization of bisallenes 1 to deliver a reactive cycloheptadiene, which concomitantly undergoes a regioselective [4 + 2] cycloaddition with alkenes. A complete mechanistic study of this transformation has been undertaken including DFT calculations. Overall, the methodology presented here constitutes a new and straightforward entry to polycyclic dihydroazepine and dihydrooxepine derivatives employing catalytic methods.

Enantioselective and Divergent Syntheses of Alstoscholarisines A, E and Their Enantiomers.

Concise, enantioselective, and divergent syntheses of alstoscholarisines A and E are presented in 8 and 9 steps, respectively; alstoscholarisine E has never been accessed before. A boron-mediated aldol reaction and Rh-catalyzed cycloisomerization were exploited to access stereoisomers 8 and 9 as key intermediates. The challenging sterically congested alstoscholarisine core was furnished by a reductive transannular cyclization in the final steps. This strategy was also used for the syntheses of enantiomers of alstoscholarisines A and E.

Total synthesis of laulimalide: synthesis of the northern and southern fragments.

The first stage in the development of a synthetic route for the total synthesis of laulimalide (1) is described. Our retrosynthetic analysis envisioned a novel macrocyclization route to the natural product by using a Ru-catalyzed alkene-alkyne coupling. This would be preceded by an esterification of the C19 hydroxyl group, joining together two equally sized synthons, the northern fragment 7 and the southern fragment 8. Our first generation approach to the northern fragment entailed a key sequential Ru/Pd coupling sequence to assemble the dihydropyran. The key reactions proceeded smoothly, but the inability to achieve a key olefin migration led to the development of an alternative route based on an asymmetric dinuclear Zn-catalyzed aldol reaction of a hydroxyl acylpyrrole. This key reaction led to the desired diol adduct 66 with excellent syn/anti selectivity (10:1), and allowed for the successful completion of the northern fragment 7. The key step for the synthesis of the southern fragment was a chemoselective Rh-catalyzed cycloisomerization reaction to form the dihydropyran ring from a diyne precursor. This reaction proved to be selective for the formation of a six-membered ring, over a seven. The use of an electron-deficient bidentate phosphine allowed for the reaction to proceed with a reduced catalyst loading.

Concise and Enantioselective Total Synthesis of 15-Deoxy-Δ12,14-Prostaglandin J2

The concise and enantioselective synthesis of 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) has been accomplished in 11 steps from a known alcohol. The key step of the synthesis involves an asymmetric Rh-catalyzed cycloisomerization of ene-ynone, followed by an olefin isomerization.

Stereoselective Ir(iii)-catalyzed dimerization reaction of enynes: an entry to functionalized polyunsaturated and cyclic systems

The Ir(III) complex [Ir(2)H(2)I(3)((rac)-Binap)(2)](+)I(-) efficiently promotes the selective dimerization of 1,6-, 1,7-enynes and functionalized alkynes. This catalytic process results in the formation of head-to-head isomers with (E)-stereoselectivity. Subsequent Rh-catalyzed cycloisomerization under reductive conditions led to the corresponding 1,2-dialkylidenecyclopentane derivatives.

Evaluating transition-metal-catalyzed transformations for the synthesis of laulimalide.

Laulimalide is a structurally unique 20-membered marine macrolide displaying microtubule stabilizing activity similar to that of paclitaxel and the epothilones. The use of atom-economical transformations such as a Rh-catalyzed cycloisomerization to form the endocyclic dihydropyran, a dinuclear Zn-catalyzed asymmetric glycolate aldol reaction to prepare the syn 1,2-diol, and an intramolecular Ru-catalyzed alkene-alkyne coupling to build the macrocycle enabled us to synthesize laulimalide via an efficient and convergent pathway. The designed synthetic route also allowed us to prepare an analogue of the natural product that possesses significant cytotoxic activity.

Rh‐ and Pt‐catalyzed cycloisomerization of enynes derived from terpenes

AbstractThe Rh‐catalyzed cycloisomerization of new terpenoid derivatives featuring an O‐tethered enyne unexpectedly leads to polycyclic derivatives containing an inner cyclopropane ring or a diene moiety, depending on the structure of the enyne, as observed in the PtCl2‐catalyzed processes. Copyright © 2008 John Wiley & Sons, Ltd.

Rh-catalyzed kinetic resolution of enynes and highly enantioselective formation of 4-alkenyl-2,3-disubstituted tetrahydrofurans.

Rh-catalyzed cycloisomerization of enynes ether with a substituent at the allylic position was examined using (rac)-BINAP, and excellent selectivity was observed. When enantiomerically pure BINAP was used as the ligand, a process that combines kinetic resolution and diastereoselectivity together was developed, in which an enantiomeric product with multiple stereogenic centers was obtained in >99% ee from a racemic starting material via single step, and half of the remaining starting material was recovered in >99% ee, also.

The First Highly Enantioselective Rh-Catalyzed Enyne Cycloisomerization This work was supported by an NIH grant, a Dreyfus Teaching-Scholar Award, and a DuPont Young Faculty Award. P.C. acknowledges the Dalalian Fellowship from the Department of Chemistry of the Pennsylvania State University. We acknowledge a generous loan of precious metals from Johnson Matthey Inc. and a gift of chiral-phase GC columns from

Adding a silver salt to the catalyst [{Rh(diphos)Cl}2] in a noncoordinating solvent in the presence of an enyne substrate resulted in the first highly enantioselective Rh-catalyzed cycloisomerization of 1,6-enynes to give 1,4-diene products with up to 98 % ee in moderate to excellent yields [Eq. (1)]. (diphos=1,2-bis(diphenylphosphanyl)ethane.)