Reported herein is that the use of catalytic quantities of hypervalent iodine reagents (phenyliodine diacetate or Dess–Martin periodinane) allows the rapid and stereoselective formation of cyclobutanes under very mild reaction conditions. The presence of a fluorinated solvent is essential for the success of these reactions which form unsymmetrical tri- and tetrasubstituted cyclobutanes through a heterodimerization process involving two different alkenes.

Reported herein is that the use of catalytic quantities of hypervalent iodine reagents (phenyliodine diacetate or Dess–Martin periodinane) allows the rapid and stereoselective formation of cyclobutanes under very mild reaction conditions. The presence of a fluorinated solvent is essential for the success of these reactions which form unsymmetrical tri- and tetrasubstituted cyclobutanes through a heterodimerization process involving two different alkenes.

The total synthesis of dehydromicrosclerodermin B and microsclerodermin J is described. Efficient approaches to the unusual amino acids in the target molecules were developed on the basis of a Negishi coupling (for Trp-2-CO₂H) and Blaise reaction (for Pyrr). An incorrect assignment of the pyrrolidinone stereochemistry of both compounds was confirmed by synthesizing epimers of the proposed structures. The spectroscopic data of these epimers were in complete agreement with those for the naturally derived material.

The total synthesis of dehydromicrosclerodermin B and microsclerodermin J is described. Efficient approaches to the unusual amino acids in the target molecules were developed on the basis of a Negishi coupling (for Trp-2-CO₂H) and Blaise reaction (for Pyrr). An incorrect assignment of the pyrrolidinone stereochemistry of both compounds was confirmed by synthesizing epimers of the proposed structures. The spectroscopic data of these epimers were in complete agreement with those for the naturally derived material.

Reported herein is the use of catalytic [{Ir(cod)Cl}₂] to facilitate hydrogen-borrowing reactions of ketone enolates with methanol at 65 °C. An oxygen atmosphere accelerates the process, and when combined with the use of a bulky monodentate phosphine ligand, interrupts the catalytic cycle by preventing enone reduction. Subsequent addition of pro-nucleophiles to the reaction mixture allowed a one-pot methylenation/conjugate addition protocol to be developed, which greatly expands the range of products that can be made by this methodology.

Reported herein is the use of catalytic [{Ir(cod)Cl}₂] to facilitate hydrogen-borrowing reactions of ketone enolates with methanol at 65 °C. An oxygen atmosphere accelerates the process, and when combined with the use of a bulky monodentate phosphine ligand, interrupts the catalytic cycle by preventing enone reduction. Subsequent addition of pro-nucleophiles to the reaction mixture allowed a one-pot methylenation/conjugate addition protocol to be developed, which greatly expands the range of products that can be made by this methodology.

The rhodium-catalyzed methylation of ketones has been accomplished using methanol as the methylating agent and the hydrogen-borrowing method. The sequence is notable for the relatively low temperatures that are required and for the ability of the reaction system to form α-branched products with ease. Doubly alkylated ketones can be prepared from methyl ketones and two different alcohols by using a sequential one-pot iridium- and rhodium-catalyzed process.

A concise synthesis of the biologically active alkaloid berberine is reported, and a versatile palladium-catalyzed enolate arylation is used to form the isoquinoline core. The overall yield of 50 % is a large improvement over the single, previous synthesis. By design, this modular route allows the rapid synthesis of other members of the protoberberine family (e.g., pseudocoptisine and palmatine) by substitution of the readily available aryl bromide and ketone coupling partners. Moreover, by combining enolate arylation with in situ functionalization, substituents can be rapidly and regioselectively introduced at the alkaloid C13 position, as demonstrated by the total synthesis of dehydrocorydaline. The avoidance of electrophilic aromatic substitution reactions to make the isoquinoline allows direct access to analogues possessing more varied electronic properties, such as the fluorine-containing derivative synthesized here.

The rhodium-catalyzed methylation of ketones has been accomplished using methanol as the methylating agent and the hydrogen-borrowing method. The sequence is notable for the relatively low temperatures that are required and for the ability of the reaction system to form α-branched products with ease. Doubly alkylated ketones can be prepared from methyl ketones and two different alcohols by using a sequential one-pot iridium- and rhodium-catalyzed process.

A concise synthesis of the biologically active alkaloid berberine is reported, and a versatile palladium-catalyzed enolate arylation is used to form the isoquinoline core. The overall yield of 50 % is a large improvement over the single, previous synthesis. By design, this modular route allows the rapid synthesis of other members of the protoberberine family (e.g., pseudocoptisine and palmatine) by substitution of the readily available aryl bromide and ketone coupling partners. Moreover, by combining enolate arylation with in situ functionalization, substituents can be rapidly and regioselectively introduced at the alkaloid C13 position, as demonstrated by the total synthesis of dehydrocorydaline. The avoidance of electrophilic aromatic substitution reactions to make the isoquinoline allows direct access to analogues possessing more varied electronic properties, such as the fluorine-containing derivative synthesized here.

This review highlights key aspects of the Tethered Aminohydroxylation from its discovery to its current incarnation, which employs N,O-acylated derivatives as reoxidants for osmium. The potential and generality of this reaction has been demonstrated by its application in the synthesis of several natural products.

A new strategy that employs an exocyclic stereocenter to effect diastereocontrol in the tethered aminohydroxylation (TA) reaction is applied to the stereoselective synthesis of a range of amino alcohols in good to excellent yields, and with anti selectivities of up to 20:1. The influence of the reaction conditions and substrate parameters on the level of diastereocontrol is described. Furthermore, an “inside alkoxy” model is employed to rationalize the sense and degree of stereoselectivity observed in these systems.

1,2-Amino alcohols are high-value, versatile functional groups that are found in scores of biologically active molecules and other interesting synthetic targets such as ligands and auxiliaries. Given their prominent position within organic compounds of import, it is no surprise to note that many routes have been developed to access this motif and there are many different starting points from which a synthetic chemist might embark on a synthesis. However, one particular approach stands out from the others, and this is the direct conversion of an alkene to a vicinal amino alcohol derivative (oxyamination). Research in this field has been particularly active in recent years and many interesting new methodologies have been reported. The purpose of this review is to give the reader a tour of the methods that have emerged in the last few years so one can appreciate the myriad of different metals and reagents that can accomplish the oxyamination of alkenes. There are still many challenges to be overcome and, herein, we also outline the areas that are ripe for further development and which bode well for the future.

A general route to prepare substituted, saturated five-membered heterocycles has been developed. The application of a wide range of starting materials to the osmium-catalyzed oxidative cyclization reaction is described. Diols, hydroxy-amides, hydroxy-sulfonamides, and carbamates all cyclize in moderate to excellent yields to give cis-tetrahydrofurans and pyrrolidines, depending upon the position of the heteroatoms in the starting materials. These cyclizations all proceed with near total selectivity for the cis-heterocycles, and with stereospecific introduction of a hydroxy group adjacent to the ring. Moreover, routes to enantiopure starting materials are described, which give enantiopure products upon cyclization. Catalyst loadings of as low as one mol percent have been successfully employed for this transformation.

Olefin metathesis has been established as an important and general reaction in synthetic organic chemistry. Recently, it has attracted interest as a powerful tool for the construction of aromatic heterocycles. The importance of heteroaromatic motifs in medicinal chemistry and biology, as well as the efficiency and wealth of metathesis transformations, have resulted in significant success in this rapidly developing area.