Chemospecific Cyclizations of α-Carbonyl Sulfoxonium Ylides on Aryls and Heteroaryls.

The functionalization of aryl and heteroaryls using α-carbonyl sulfoxonium ylides without the help of a directing group has remained so far a neglected area, despite the advantageous safety profile of sulfoxonium ylides. Described herein are the cyclizations of α-carbonyl sulfoxonium ylides onto benzenes, benzofurans and N-p-toluenesulfonyl indoles in the presence of a base in HFIP, whereas pyrroles and N-methyl indoles undergo cyclization in the presence of an iridium catalyst. Significantly, these two sets of conditions are chemospecific for each groups of substrates.

Intramolecular Thioether Migration in the Rhodium-Catalyzed Ene-Cycloisomerization of Alkenylidenecyclopropanes by a Metal-Mediated ß-Sulfide Elimination.

Reported is the first example of a rhodium-mediated ß-sulfide elimination, which represents a new mode of reactivity for late-transition-metal chemistry. This serendipitous discovery facilitates an ene-cycloisomerization of allylic-sulfide-containing alkenylidenecyclopropanes (ACPs) to afford five-membered carbo- and heterocyclic rings with concomitant intramolecular thioether migration. Interestingly, similar selectivity is obtained with both E- and Z-allylic sulfides and the reaction is also feasible with an allylic selenide. Mechanistic studies are consistent with an inner-sphere transfer of the sulfide, which is remarkable given the propensity for sulfides to poison transition-metal catalysts. Finally, this type of atom-economical rearrangement is envisioned to prompt the development of related processes given the utility of sulfides in target-directed synthesis.

The isolation and characterization of a rhodacycle intermediate implicated in metal-catalyzed reactions of alkylidenecyclopropanes.

The isolation and characterization of a rhodacycle intermediate implicated in rhodium-catalyzed reactions of alkylidenecyclopropanes (ACPs) is described. The structure of the metallacycle was unambiguously determined by X-ray crystallography and is catalytically competent in the rhodium-catalyzed carbocyclization and ene-cycloisomerization reactions of ACPs. This work represents a rare example of the isolation of a metallacycle in a metal-catalyzed higher-order carbocyclization reaction and thereby provides important insight into the ligand requirements for the insertion of π-components. Furthermore, it serves as a convenient synthon for the development of challenging higher-order carbocyclization reactions, as exemplified by the reaction with an activated allene.

Diastereoselective rhodium-catalyzed ene-cycloisomerization reactions of alkenylidenecyclopropanes: total synthesis of (-)-α-kainic acid.

The rhodium-catalyzed ene-cycloisomerization of alkenylidenecyclopropanes provides an atom-economical approach to five-membered carbo- and heterocycles that contain two new stereogenic centers. A key and striking feature of this protocol is that the alkene geometry does not impact the efficiency and diastereocontrol, which provides excellent synthetic versatility. For instance, (E)- and (Z)-allylic alcohols furnish the corresponding aldehydes with similar efficiency and selectivity. This process facilitates the construction of a key intermediate in an eight-step total synthesis of (-)-α-kainic acid.

Stereoselective transition metal-catalysed higher-order carbocyclisation reactions.

Transition metal-catalysed higher-order carbocyclisation reactions represent an important class of reactions due to their ability to construct complex polycyclic systems in a highly selective and atom-economical fashion. A key and striking feature with these transformations is the dichotomy in reactivity that a substrate displays with different transition metal complexes, which is akin to the manner enzymes direct terpene biosynthesis. This tutorial review details the historical development of higher-order carbocyclisation reactions, specifically the variants of [m+2+2] that involve carbon-based pi-systems, where m = 2, 3 and 4, in the context of critical developments with various transition metal complexes.

Intermolecular rhodium-catalyzed [3+2+2] carbocyclization of alkenylidenecyclopropanes with activated alkynes: regio- and diastereoselective construction of cis-fused bicycloheptadienes.

Polycyclic structures that contain seven-membered carbocycles constitute important structural motifs that are ubiquitous in several classes of bioactive natural products. We have developed the first regio- and diastereoselective intermolecular rhodium-catalyzed [3+2+2] carbocyclization of carbon- and heteroatom-tethered alkenylidenecyclopropanes with mono- and disubstituted alkynes for the construction of cis-fused bicycloheptadienes. This study delineates some of the critical features for controlling regioselectivity in this process and demonstrates that E-alkenes can be incorporated in a stereospecific manner to afford products with up to three new stereogenic centers. The latter feature is particularly significant given that related carbocyclization reactions are often limited in this respect.

A concise total synthesis of pyrovellerolactone using a rhodium-catalyzed [(3 + 2) + 2] carbocyclization reaction.

A concise and highly convergent three-step total synthesis of the lactarane natural product, pyrovellerolactone, is described. The key step involves a regio- and diastereoselective rhodium-catalyzed [(3 + 2) + 2] carbocyclization of an alkenylidenecyclopropane with a 4-hydroxybut-2-ynoate followed by an in situ intramolecular lactonization to generate the tricyclic core in a single operation. This represents the first example of a higher-order [3 + 2 + 2] carbocyclization reaction in total synthesis, which is likely to provide an important strategy for the construction of related targets within this sesquiterpene family.