Lewis Acid-promoted Rearrangement Research Articles

Route to 1,2,4- and 1,2,5-oxadiazole ring assemblies via a one-pot condensation/oxidation protocol

A novel one-pot approach for the synthesis of 1,2,4- and 1,2,5-oxadiazole ring assemblies has been developed. The synthetic strategy involves the condensation of furoxanyl amidoximes with aldehydes and subsequent iodine-mediated oxidation of the intermediate 1,2,4-oxadiazolines. The analogous reaction of 4-aminofuroxanyl-3-carboxamidoxime results not only in formation of the 1,2,4-oxadiazole subunit, but also rearrangement of the furoxan ring to the furazan one, which is the first example of a Lewis acid-promoted rearrangement in a furoxan series.

Synthesis of novel carbohydrate mimetics via 1,2-oxazines

The combination of lithiated alkoxyallenes with carbohydrate-derived nitrones constitutes a flexible entry to highly functionalized enantiopure 1,2-oxazine derivatives. They can be used as precursors for acyclic and cyclic carbohydrate-like products such as amino sugar alcohols, azetidine and pyrrolidine derivatives. The Lewis acid-promoted rearrangement of 1,3-dioxolanyl-substituted 1,2-oxazines to bicyclic compounds allows an efficient route to novel amino pyran and oxepane derivatives. After subsequent transformations, new carbohydrate mimetics or “real” carbohydrates were obtained in good yield and often in a stereodivergent fashion. These compounds have already been employed for the preparation of unusual di- and trisaccharide derivatives. Several of the products prepared showed interesting biological activities, e.g., as L- and P-selectin inhibitors with IC50 values in the subnanomolar range.

Stereoselective synthesis of 2-deoxy-pyranosides via the Lewis acid-promoted rearrangement of 2,3-anhydrothiosugars

Stereoselective synthesis of 2-deoxy-pyranosides via the Lewis acid-promoted rearrangement of 2,3-anhydrothiosugars

ChemInform Abstract: Ring-Enlarging Cyclopentene Annulations.

Abstract Ethynylation of 2-[(2,2-dialkoxy)ethyl]cycloalkanones followed by Lewis acid-promoted rearrangement occasions cyclopentene annulation with concomitant one-carbon ring expansion of the starting cycloalkanone.

ChemInform Abstract: Lewis Acid-Promoted 3-Aza-Cope Rearrangement of N-Alkyl-N- allylanilines.

The 3-aza-Cope rearrangement of N-alkyl-N-allylaniline substrates, which required 250 o C to proceed thermelly, was promoted by Lewis acid reagents at 111-140 o C. Systematic studies of this reaction were performed to examine a number of reaction variables such as concentration, the stoichiometry of the Lewis acid with the substrate, the optimum temperature for rearrangement, and the type of Lewis acid reagent. Of the many Lewis acids investigated, ZnCl 2 (140 o C) and Et 2 O-BF 3 (111 o C) were the most generally successful reagents for promoting the aromatic 3-aza-Cope rearrangement. With respect to substrate variation, the presence of a methoxy substituent para to the N-allyl group slowed the reaction slightly, while a meta substituent accelerated the rate of [3.3] rearrangement and produced moderate site selectivity on the aromatic ring. Lewis acid-promoted rearrangement of an unsymmetrically substituted allyl moiety resulted in [3.3] sigmatropic rearrangement to give the 1-hexen-3-yl substituent on the aromatic ring. Overall, both ZnCl 2 , and Et 2 O.BF 3 were shown to efficiently accelerate the regiospecific 3-aza-Cope rearrangement of N-alkyl-N-allylanilines for the purpose of forming a carbon-carbon bond between a secondary alkyl substituent and an aromatic ring

Lewis Acid-Promoted Rearrangement of 2,3-Epoxy Alcohol Derivatives: Stereochemical Control and Selective Formation of Two Types of Chiral Quaternary Carbon Centers from the Single Carbon Skeleton

The Lewis acid-promoted rearrangement of 2,2,3,3-tetrasubstituted 2,3-epoxy alcohols with several kinds of protecting groups was investigated. When SnCl4 is used as a Lewis acid, the reaction proceeds in a regio- and stereo-controlled manner to afford two types of carbonyl compounds selectively from a single 2,3-epoxy alcohol only by changing the protecting group of the alcohol. The method was then applied to the formation of two types of acyclic and cyclic quaternary carbon centers from the single compound in optically active forms.

Synthesis of the floresolide B hydroquinone lactone core using ring-closing metathesis

The hydroquinone lactone core of the floresolides was synthesized through a ring-closing metathesis (RCM) approach. Optimal RCM efficiency was obtained at higher reaction concentration. An unexpected Lewis acid-promoted rearrangement of the hydroquinone and other observations relevant to on-going total synthesis efforts are discussed.

Silicon-guided rearrangement of 10-methyl-4,5-epoxydecalins. Methyl versus methylene migration

The Lewis acid-promoted rearrangement of two 10-methyl-4,5-epoxydecalins bearing a trimethylsilyl (TMS) group on C-1 or C-9 has been studied. Migration of the C-9 methylene group to C-5 is the major reaction pathway when the TMS and the oxirane groups are on the same ring while methyl migration results exclusively when they are on different rings.

Study of the Lewis acid-promoted rearrangement of 2-aryl-2,3-epoxy acylates

The reaction of 2-aryl-2,3-epoxy acylates with Lewis acids was examined in detail. Cyclic 2-aryl-2,3-epoxy acylates afforded the rearranged products via the C2-carbocation intermediates obtained by the C2-cleavage of the oxirane rings. On the other hand, acyclic 2-aryl-2,3-epoxy acylates gave the rearranged products via the phenonium ion intermediates obtained by the C3-cleavage of the oxirane rings. The method was also applied to the synthesis of the optically active benzylic quaternary carbon center.

Lewis acid-promoted 3-aza-Cope rearrangement of N-alkyl-N-allylanilines

The 3-aza-Cope rearrangement of N-alkyl-N-allylaniline substrates, which required 250 o C to proceed thermelly, was promoted by Lewis acid reagents at 111-140 o C. Systematic studies of this reaction were performed to examine a number of reaction variables such as concentration, the stoichiometry of the Lewis acid with the substrate, the optimum temperature for rearrangement, and the type of Lewis acid reagent. Of the many Lewis acids investigated, ZnCl 2 (140 o C) and Et 2 O-BF 3 (111 o C) were the most generally successful reagents for promoting the aromatic 3-aza-Cope rearrangement. With respect to substrate variation, the presence of a methoxy substituent para to the N-allyl group slowed the reaction slightly, while a meta substituent accelerated the rate of [3.3] rearrangement and produced moderate site selectivity on the aromatic ring. Lewis acid-promoted rearrangement of an unsymmetrically substituted allyl moiety resulted in [3.3] sigmatropic rearrangement to give the 1-hexen-3-yl substituent on the aromatic ring. Overall, both ZnCl 2 , and Et 2 O.BF 3 were shown to efficiently accelerate the regiospecific 3-aza-Cope rearrangement of N-alkyl-N-allylanilines for the purpose of forming a carbon-carbon bond between a secondary alkyl substituent and an aromatic ring

Ring-enlarging cyclopentene annulations

Ethynylation of 2-[(2,2-dialkoxy)ethyl]cycloalkanones followed by Lewis acid-promoted rearrangement occasions cyclopentene annulation with concomitant one-carbon ring expansion of the starting cycloalkanone.