Phase-transfer-catalysed asymmetric synthesis of 2,2-disubstituted 1,4-benzoxazin-3-ones.

1,4-Benzoxazin-3-one is a scaffold which is found in a variety of biologically active molecules. Because of its unique structure and drug-like activities, 1,4-benzoxazin-3-ones have been widely used in drug discovery. However, just a few methods have been developed to access these molecules by catalytic asymmetric synthesis. We report herein the phase-transfer-catalysed asymmetric alkylation of 2-aryl-1,4-benzoxazin-3-ones as a new way for the highly enantioselective synthesis of 2,2-disubstituted 1,4-benzoxazin-3-ones.

Alkylative kinetic resolution of vicinal diols under phase-transfer conditions: a chiral ammonium borinate catalysis.

Herein, we report the first alkylative kinetic resolution of vicinal alcohols realized by cooperative use of a chiral quaternary ammonium salt and an achiral borinic acid. In addition, a catalytic regioselective alkylation of a secondary alcohol in the presence of an unprotected primary one is presented, emphasizing the unique selectivity and potential of this ammonium borinate catalysis.

Enantioselective Total Synthesis of (+)-Lysergol: A Formal anti-Carbopalladation/Heck Cascade as the Key Step.

The enantioselective synthesis of (+)-lysergol was completed in 12 steps and an overall yield of 13% starting from a known literature precursor. The key step relies on a domino reaction containing a formal anti-carbopalladation, which is terminated by a ß-silyl-directed Heck reaction. During this transformation, the two six-membered rings of the ergot scaffold are formed in a completely stereospecific manner.

[4+3] Cycloaddition of Donor-Acceptor Cyclopropanes with Amphiphilic Benzodithioloimine as Surrogate for ortho-Bisthioquinone.

Donor-acceptor cyclopropanes were reacted with amphiphilic benzodithioloimine to give seven-membered heterocycles with two sulfur atoms. Formally, this transformation can be regarded as a [4+3] cycloaddition reaction of the three-membered ring and ortho-bisthioquinone. The benzodithioloimine serves as a surrogate for this highly reactive diene. The structure of the products was confirmed by X-ray crystallography. Broad signals in (13) C NMR studies suggest that several conformers, slowly interconverting on the NMR timescale, are present at room temperature.

Intramolecular Formal anti-Carbopalladation/Heck Reaction: Facile Domino Access to Carbo- and Heterooligocyclic Dienes.

An intramolecular domino process consisting of a formal anti-carbopalladation followed by Heck reaction is realized. Complex oligo(hetero)cyclic scaffolds are efficiently obtained in one synthetic step from easily obtainable enyne precursors. In contrast to common syn-carbopalladation reactions of alkyne units, the carbopalladation employed here is designed to afford an anti-arrangement of the two new substituents across the emerging double bond. A prerequisite is that the residues next to the alkyne should lack any ß-hydrogen atoms. The method paves the way to tri- and tetrasubstituted double-bond systems that have not been accessible by conventional Pd catalysis.

Exploiting amphiphilicity: facile metal free access to thianthrenes and related sulphur heterocycles.

Benzodithioloimines are reacted with arynes or alkynes substituted with electron-withdrawing groups to afford the corresponding thianthrene or benzo[b][1,4]dithiine derivatives. The transformation takes place under mild reaction conditions without any transition metal. Furthermore, the reaction mode could be expanded to 2-thiocyanatopyrroles yielding pyrrolothiazoles.

Activation of aryl thiocyanates followed by aryne insertion: access to 1,2-thiobenzonitriles.

Palladium-catalyzed activation of carbon-sulfur bonds allows aryne insertion into aryl thiocyanates to generate new C-SAr and C-CN bonds in one step. The readily available starting materials make this method efficient in generating a variety of 1,2-thiobenzonitriles. By choosing an oxygen atmosphere the yields are increased and side reactions are minimized.

Formal anti-carbopalladation reactions of non-activated alkynes: requirements, mechanistic insights, and applications.

Formal anti-carbopalladation reactions of CC triple bonds are uncommon, but highly useful transformations. Alkynes can be designed to give anti-carbopalladation products. Prerequisite is the exclusion of other reaction pathways to provoke the cis-trans isomerization of the syn-carbopalladation intermediate. Detailed mechanistic studies of this crucial step by experimental and computational means were performed. Application of an intramolecular version for the synthesis of oligocyclic compounds and substituted dibenzofurans is also described.

π-Helicenes truncated to a minimum: access through a domino approach involving multiple carbopalladations and a Stille coupling.

A novel type of π-helicenes is reported, in which the π-system is truncated to an all-s-cis all-Z oligoene chain. A domino sequence was developed, consisting of up to four consecutive carbopalladation reactions and a terminal Stille cross-coupling, to generate these entities in one step from the respective linear oligoynes. Despite the minimal π-system, very high optical rotation values were encountered for the single enantiomers. X-ray crystallography confirmed their screw-shaped structure.

Template control over dimerization and guest selectivity of interpenetrated coordination cages.

We have previously shown that the self-assembly of dibenzosuberone-based bis-monodentate pyridyl ligands L(1) with Pd(II) cations leads to the quantitative formation of interpenetrated coordination cages [BF4@Pd4L(1)8]. The BF4(-) anion inside the central cavity serves as a template, causing the outer two pockets to show a tremendous affinity for allosteric binding of two small chloride anions. Here we show that derivatization of the ligand backbone with a bulky aryl substituent allows us to control the dimerization and hence the guest-binding ability of the cage by the choice of the templating anion. Steric constraints imposed by L(2) prevent the large BF4(-) anion from serving as a template for the formation of interpenetrated double cages. Instead, a single isomer of the monomeric cage [Pd2L(2)4] is formed. Addition of the small anionic template Cl(-) permits dimerization, yielding the interpenetrated double cage [Cl@Pd4L(2)8], whose enlarged outer pockets show a preference for the binding of large anions such as ReO4(-).

A ridge walk between reaction modes: an unprecedented Pd-catalyzed domino sequence of diynyl-substituted bromoarenes.

Diynyl-substituted bromoarenes underwent a novel Pd-catalyzed domino reaction to provide benzofurans, pyridinofurans, isochromenes, and indole derivatives. Slight changes of the substrate push the reaction in another direction resulting in benzene annulation.

Hybrids of sugars and aromatics: A Pd-catalyzed modular approach to chromans and isochromans.

Herein we describe the synthesis of highly substituted chromans and isochromans using carbohydrates as starting materials. The key step of our synthetic approach is the annelation of the benzene moiety via a highly efficient Pd-catalyzed domino reaction. This powerful approach led to a small library of highly substituted chromans and isochromans by making use of a variety of different diynes and bromoglycals. We investigated several Pd-catalysts in order to improve the yields and to enlarge the scope of the domino reaction. Furthermore, we elucidated the mechanistic picture of the reaction with isotope-labelling experiments. Most probably the reaction proceeds via an oxidative addition followed by two carbopalladation steps and a final cyclization reaction.

Domino access to highly substituted chromans and isochromans from carbohydrates.

Herein we describe the synthesis of highly substituted chromans and isochromans using carbohydrates as starting materials. Our approach makes use of a Pd-catalyzed domino reaction consisting of oxidative addition, followed by two carbopalladation steps and completed by a cyclization to annelate the benzene moiety. The versatility of this route has been demonstrated by a small library of highly substituted chromans and isochromans.