Side reactions associated with metallocarbenes can be a potential limitation of this class of reactions for specific substrates. For example, substrates with appropriately positioned C-H bonds may undergo intramolecular C-H insertion in preference to carbonyl ylide formation (Eq. 13). A judicious choice of catalyst can lead to selective carbonyl ylide formation.
Rhodium carboxylate complexes are by far the most common catalysts used for cycloadditions of carbonyl ylides, although other metal complexes have seen limited application. Chiral rhodium carboxylates or those employing more exotic ligands may be obtained from Rh2(OAc)4 by ligand exchange. Catalyst loadings are typically in the range 0.2-5 mol%. In general for intermolecular reactions, it is important to maintain an excess of dipolarophile throughout the reaction to avoid side reactions. This can be achieved by employing an excess of the dipolarophile or by slow addition (by syringe pump) of the diazocarbonyl compound to a stirred solution of the catalyst and dipolarophile. Reactions are typically carried out in an inert atmosphere, and the presence of a drying agent may be necessary in some cases. A wide variety of solvents have been employed in these reactions; ionic liquids can facilitate separation of the cycloadduct from the catalyst and catalyst recovery.
Helps in the synthesis of 1,3 diols.
For example, thermal decomposition of epoxides can produce carbonyl ylides, which can undergo cycloaddition in an intramolecular sense. Although this method possesses high atom economy, yields are often low (Eq. 16).
Organic Synthesis and Carbon-Carbon Bond Forming Reactions
AB - Detailed in this account are our efforts toward efficient oxacycle syntheses. Two complementary approaches are discussed, with both employing chemoselective allyl ether activation and rearrangement as the key step. Vinyl substituted oxiranes and oxetanes provide a single step access to dihydropyrans and tetrahydrooxepines. Oxiranes proved to be poor substrates, while oxetanes were slightly better. An alternative approach using substituted allyl ethers proved successful and addressed the limitations encountered in the ring expansions.
Methods - Synthesis & Techniques
Direct cyclopropanation of the dipolarophile can also be a significant issue in these reactions. Since carbonyl ylide formation is often reversible, an excess of dipolarophile is usually employed to encourage cycloaddition.
[Synthesis of -pyridone derivatives with pyridinium ylide].
The scope of intermolecular cycloadditions is somewhat broader than that for intramolecular reactions, because the preparation of starting materials is simpler. Still, in the majority of cases the diazo group and carbonyl group forming the ylide are found in the same molecule (i.e., the carbonyl ylides are cyclic). For example, a cyclic, ketone-derived carbonyl ylide is involved in the -selective cycloaddition reaction in Eq. 10.
[Synthesis of -pyridone derivatives with pyridinium ylide]
Nucleophilic substitution reactions of 2,3-epoxy alcohols, easily prepared via Sharpless asymmetric epoxidation chemistry, offer access to a wide variety of enantiomerically pure compounds. In this communication, we describe the use of a Payne rearrangement to control regioselectivity in the ring-opening of a series of 2,3-epoxy alcohols with dimethylsulfoxonium methylide to yield diastereomerically and/or enantiomerically pure disubstituted tetrahydrofuran rings. The factors influencing the success and substitution pattern of the THF ring products are discussed, including steric, electronic, and solvent effects.
Synthesis and pyrolysis of cyclic sulfonium ylides
By a sidearm approach, camphor-derived sulfur ylides 1 were designed and synthesized for the cyclopropanation of electron-deficient alkenes and epoxidation of aldehydes. Under the optimal conditions, the exo-type sulfonium salts 4a and 4b reacted with -aryl-,β-unsaturated esters, amides, ketones, and nitriles to give 1,3-disubstituted-2-vinylcyclopropanes with high diastereoselectivities and enantioselectivities. When the endo-type sulfonium salts 5a and 5b were used, the diastereoselectivities were not changed, whereas the absolute configurations of the products became the opposite to those of the reactions of 4a and 4b. An ylide cyclopropanation of chalcone derivatives with phenylvinyl bromide in the presence of catalytic amount of chiral sulfonium salts 4b and 5b has been developed. The sidearmed hydroxyl group was found to play a key role in the control of enantioselectivity and diastereoselectivity. The origins of the high diastereoselectivity and enantioselectivity were also studied by density functional theory calculations, which reveal the importance of the hydrogen-bonding between the sidearmed hydroxyl group and the substrate in determining the diastereoselectivity and enantioselectivity. The ylides 1 were also successfully applied for the epoxidation of aromatic aldehydes.