Rhodium(II)-Catalyzed Enantioselective Intermolecular Aziridination of Alkenes.

C4-Symmetrical dirhodium(II) tetracarboxylates are highly efficient catalysts for the asymmetric intermolecular aziridination of substituted alkenes with sulfamates. The reaction proceeds with high levels of efficiency and chemoselectivity to afford aziridines with excellent yields of up to 95% and enantiomeric excesses of up to 99%. The scope of the alkene aziridination includes mono-, di-, and trisubstituted olefins as well as the late-stage functionalization of complex substrates. The reaction can be performed on a gram-scale with a catalyst loading of 0.1 mol %. Our DFT study led us to propose a two-spin-state mechanism, involving a triplet Rh-nitrene species as key intermediate to drive the stereocontrolled approach and activation of the substrate.

Asymmetric Synthesis of Enantiopure Pyrrolidines by C(sp3 )-H Amination of Hydrocarbons.

The asymmetric synthesis of enantiopure pyrrolidines is reported via a streamlined strategy relying on two sequential C-H functionalizations of simple hydrocarbons. The first step is a regio- and stereoselective catalytic nitrene C-H insertion. Then, a subsequent diastereoselective cyclization involving a 1,5-hydrogen atom transfer (HAT) from a N-centered radical leads to the formation of pyrrolidines that can then be converted to their free NH-derivatives.

Asymmetric Intramolecular Buchner Reaction: From High Stereoselectivity to Coexistence of Norcaradiene, Cycloheptatriene, and an Intermediate Form in the Solid State.

Bicyclic compounds bearing a quaternary stereogenic center have been obtained using asymmetric intramolecular Buchner reaction with excellent yields and level of enantioselectivity. X-ray crystallography determination of the absolute configuration of one product has led to the serendipitous observation of an unusual behavior within the crystal structure, with equilibrating norcaradiene and cycloheptatriene valence isomers at the solid state, as well as an even more unexpected intermediate form. DFT calculations were performed to support these observations.

Catalytic Enantioselective Intermolecular Benzylic C(sp3 )-H Amination.

A practical general method for asymmetric intermolecular benzylic C(sp3 )-H amination has been developed by combining the pentafluorobenzyl sulfamate PfbsNH2 with the chiral rhodium(II) catalyst Rh2 (S-tfptad)4 . Various substrates can be used as limiting components and converted to benzylic amines with excellent yields and high levels of enantioselectivity. Additional key features for the reaction are the low catalyst loading and the ability to remove the Pfbs group under mild conditions to give NH-free benzylic amines.

Late-stage C-H amination of abietane diterpenoids.

This study aims at highlighting the synthetic versatility of the rhodium-catalyzed C-H amination reactions using iodine(iii) oxidants for the late-stage functionalization of natural products. Inter- and intramolecular nitrene insertions have been performed from various abietane diterpenoids, leading to the amination of the C-3, C-6, C-7, C-11 and C-15 positions. Ca. 20 aminated compounds have been isolated with yields of up to 86% and high levels of regio-, chemo- and stereoselectivities.

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis.

Most of the polyvalent organoiodine compounds derive from iodoarenes, which are released in stoichiometric amounts in any reaction mediated by λ3- or λ5-iodanes. In parallel to the development of solid-supported reagents or reactions catalytic in iodine, a third strategy has emerged to address this issue in terms of sustainability. The atom-economy of transformations involving stoichiometric amounts of λ3- or λ5-iodanes, thus, has been improved by designing tandem reactions that allows for incorporating the aryl motif into the products through a subsequent one-pot nucleophilic addition or catalytic coupling reaction. This review summarizes the main achievements reported in this area.

Total Synthesis of (-)-Himalensine A.

The first enantioselective synthesis of (-)-himalensine A has been achieved in 22 steps. The synthesis was enabled by a novel catalytic, enantioselective prototropic shift/furan Diels-Alder (IMDAF) cascade to construct the ACD tricyclic core. A reductive radical cyclization cascade was utilized to build the B ring, and end-game manipulations featuring a molecular oxygen mediated γ-CH oxidation, a Stetter cyclization to access the pendant cyclopentenone, and a highly chemoselective lactam reduction delivered the natural product target.

Reaction of Ynamides with Iminoiodinane-Derived Nitrenes: Formation of Oxazolones and Polyfunctionalized Oxazolidinones.

This article describes the reaction of ynamides with metallanitrenes generated in the presence of an iodine(III) oxidant. N-(Boc)-Ynamides are converted to oxazolones via a cyclization reaction. The reaction is mediated by a catalytic dirhodium-bound nitrene species that first behaves as a Lewis acid. The oxazolones can be converted in a one pot manner to functionalized oxazolidinones following a regio- and stereoselective oxyamination reaction with the same nitrene reagent generated in stoichiometric amounts.

The Multiple Facets of Iodine(III) Compounds in an Unprecedented Catalytic Auto-amination for Chiral Amine Synthesis.

Iodine(III) reagents are used in catalytic one-pot reactions, first as both oxidants and substrates, then as cross-coupling partners, to afford chiral polyfunctionalized amines. The strategy relies on an initial catalytic auto C(sp(3) )-H amination of the iodine(III) oxidant, which delivers an amine-derived iodine(I) product that is subsequently used in palladium-catalyzed cross-couplings to afford a variety of useful building blocks with high yields and excellent stereoselectivities. This study demonstrates the concept of self-amination of the hypervalent iodine reagents, which increases the value of the aryl moiety.

Tandem Catalytic C(sp(3) )-H Amination/Sila-Sonogashira-Hagihara Coupling Reactions with Iodine Reagents.

A new tandem C-N and C-C bond-forming reaction has been achieved through Rh(II) /Pd(0) catalysis. The sequence first involves an iodine(III) oxidant, then the in situ generated iodine(I) by-product is used as a coupling partner. The overall process demonstrates the synthetic value of iodoarenes produced in trivalent iodine reagent mediated oxidations.

Intermolecular C-H amination of complex molecules: insights into the factors governing the selectivity.

Transition-metal-catalyzed C-H amination via nitrene insertion allows the direct transformation of a C-H into a C-N bond. Given the ubiquity of C-H bonds in organic compounds, such a process raises the problem of regio- and chemoselectivity, a challenging goal even more difficult to tackle as the complexity of the substrate increases. Whereas excellent regiocontrol can be achieved by the use of an appropriate tether securing intramolecular addition of the nitrene, the intermolecular C-H amination remains much less predictable. This study aims at addressing this issue by capitalizing on an efficient stereoselective nitrene transfer involving the combination of a chiral aminating agent 1 with a chiral rhodium catalyst 2. Allylic C-H amination of terpenes and enol ethers occurs with excellent yields as well as with high regio-, chemo-, and diastereoselectivity as a result of the combination of steric and electronic factors. Conjugation of allylic C-H bonds with the π-bond would explain the chemoselectivity observed for cyclic substrates. Alkanes used in stoichiometric amounts are also efficiently functionalized with a net preference for tertiary equatorial C-H bonds. The selectivity, in this case, can be rationalized by steric and hyperconjugative effects. This study, therefore, provides useful information to better predict the site of C-H amination of complex molecules.

Expedient construction of the [7-5-5] all-carbon tricyclic core of the Daphniphyllum alkaloids daphnilongeranin B and daphniyunnine D.

A synthetic strategy for the construction of the [7-5-5] all-carbon tricyclic core of numerous calyciphylline A-type Daphniphyllum alkaloids has been developed using a key intramolecular Pauson-Khand reaction. A subsequent base-mediated double-bond migration and a regio- and stereoselective radical late stage allylic oxygenation provide access to the substitution patterns of daphnilongeranin B and daphniyunnine D.

Asymmetric synthesis of cyclobutanones: synthesis of cyclobut-G.

A simple, efficient, and stereoselective approach has been developed for obtaining chiral cis- and trans-disubstituted cyclobutanones from readily available alkyl- and functionalized alkyl-substituted enol ethers. The usefulness of these cyclobutanones is illustrated by an enantioselective synthesis of cyclobut-G (Lobucavir).

Acid-catalyzed synthesis of bicyclo[3.n.1]alkenediones.

An acid-catalyzed Dieckmann-type reaction has been developed to access functionalized bicyclo[3.2.1]alkenediones. This methodology has been successfully extended to more substituted and larger ring homologues, providing a new and efficient route to the core of numerous attractive natural products and their analogues.

Asymmetric synthesis of functionalized, monocyclic chlorocyclobutenes.

The selective synthesis of a variety of stereopure monocyclic chlorocyclobutenes is described. These derivatives could be coupled with Grignard reagents; two dienes from coupling with vinylmagnesium bromide reacted smoothly with maleic anhydride to yield illudol-related [4 + 2] cycloadducts.

Ynol ethers from dichloroenol ethers: mechanistic elucidation through 35Cl labeling.

The mechanism of ynol ether formation from dichloroenol ethers, a decades-old transformation, has been studied by experimental and theoretical techniques to determine the relative importance of the Fritsch-Buttenberg-Wichell rearrangement (alpha-elimination) and beta-elimination in the evolution of the intermediate carbenoid.

Expedient approach to chiral cyclobutanones: asymmetric synthesis of cyclobut-G.

An efficient one-pot asymmetric synthesis of cyclobutanones from chiral enol ethers is described. The approach is illustrated with alkyl- and functionalized alkyl-substituted enol ethers (nine examples). A new enantioselective synthesis of cyclobut-G (Lobucavir) could thus be achieved.