Preorganization in highly enantioselective diaza-Cope rearrangement reaction

Crystal structure and activation entropy data indicate that H-bond directed diaza-Cope rearrangement of chiral diimines takes place with a high degree of preorganization. CD spectroscopy and HPLC data show that there is inversion of stereochemistry for the reaction with excellent enantioselectivity.     

Controlling diaza-Cope rearrangement reactions with resonance-assisted hydrogen bonds

NMR studies reveal that the equilibrium between 1 and 2 lies essentially toward 1 to the left without any detectable amount of 2. DFT computation shows that the value of K1 is about 1.4 x 10-5, and X-ray crystal structures show that the resonance-assisted hydrogen bond (RAHB) in 1 (1.66 A) is shorter than the regular hydrogen bond in 2 (1.75 A). The enormous selectivity can be explained in terms of the strength of the RAHBs in 1 compared to that of the regular hydrogen bonds in 2.     

Diastereoselective ireland-claisen rearrangement of allylic alcohols

The “chelation-controlled” Ireland-Claisen rearrangement of allylic glycolate esters is described in which the stereocontrol of the prochiral sp² sites is achieved by the allylic oxygen substitutent.     

Formation of new pyridyl substituted enamines. Observation of a diaza-Cope rearrangement

Some 2-arylthiopyridinium imides when reacted with dimethyl acetylene dicarboxylate exhibited ambident behaviour: either a 1,3-dipolar cyclization occurred followed by a ring transformation to yield pyrrolopyridines or 5-pyridyl substituted enamines were formed in a different route. Mechanistic considerations revealed that this latter unusual transformation is initiated by a Michael addition of the imide nitrogen atom of the starting pyridinium compound on the reagent, which is followed by a [3,3]-sigmatropic (‘diaza-Cope’) rearrangement. Ring opening of the pyrrolopyridine compounds by a base also yielded pyridylenamines, which proved to be positional isomers of the sigmatropic rearrangement products. The new pyridyl derivatives seem to be valuable compounds for further transformations. Thus, they can undergo thermal electrocyclization to 7-azaindoles.     

Tandem diaza-Cope rearrangement polymerization: turning intramolecular reaction into powerful polymerization to give enantiopure materials for Zn2+ sensors

[3,3]-Sigmatropic rearrangement is a powerful reaction to form C–C bonds stereospecifically; however, owing to intrinsic simultaneous bond formation and breakage, this versatile method has not been utilized in polymerization. Herein, we report a new tandem diaza-Cope rearrangement polymerization (DCRP) that can synthesize polymers with defect-free C–C bond formation from easy and efficient imine formation. A mechanistic investigation by in situ¹H NMR experiments suggests that this polymerization proceeds by a rapid DCR process, forming an enantiospecific C–C bond that occurs almost simultaneously with imine formation. This polymerization produces not only highly stable polymers against hydrolysis due to resonance-assisted hydrogen bonds (RAHBs) but also chiral polymers containing enantiopure salen moieties, which lead to high-performance Zn²⁺-selective turn-on chemosensors with up to 73-fold amplification. We also found that their optical activities and sensing performances are heavily dependent on the reaction temperature, which significantly affects the stereoselectivity of DCR.

Herein, we report a new tandem diaza-Cope rearrangement polymerization synthesizing enantiopure polymers with defect-free C–C bond formation. Furthermore, these polymers can be applied as high-performance turn-on Zn²⁺ sensors.     

Diastereoselective cobalt-assisted Ferrier-type rearrangement to construct chiral alkynyl cyclohexanones

Functionalized 1-C-alkynyl sugars are prepared from 2-acetoxy-glucal triacetate. Dicobalt complexes of these sugar acetylenes can stabilize the anomeric carbenium cations, which promote the Ferrier-type rearrangement through the 5,6-dehydro precursors to afford alkynyl cyclohexanones after decomplexation. High stereoselectivity resulted from suitable steric interaction between the C-2 O-protecting group and the alkynyl substituents. Molecular mechanism is discussed.     

Stereospecific synthesis of C2 symmetric diamines from the mother diamine by resonance-assisted hydrogen-bond directed diaza-Cope rearrangement

Sixteen diphenylethylenediamine analogues including those with electron donating, electron withdrawing, and sterically bulky substituents have been prepared in good overall yields (70-90%) and in enantiomerically pure form (>99% ee) by diaza-Cope rearrangement reaction. A single chiral mother diamine, ((R,R)-1,2-bis-(2-hydroxyphenyl)-1,2-diaminoethane), is reacted with appropriate aldehydes to form the initial diimines that rearrange to give all the product diimines in the (S,S) form. The daughter diamines are obtained by hydrolysis of the product diimines. Density functional theory computation shows that resonance-assisted hydrogen-bond is the main driving force behind all the rearrangement reactions. Chiral high performance liquid chromatography and circular dichroism spectroscopy show that the highly stereospecific rearrangement reactions take place with apparent inversion of stereochemistry.     

苯酞类化合物重排反应的研究——————3－位烷基取代苯 酞的重排反应

发现了3-正丁基苯酞在三氯化铝作用下进行重排反应生成1-甲基-5-羧基四氢萘,并提出了氢迁移的重排反应机制。研究了3-位不同烷基取代的苯酞类化合物在三氯化铝作用下的重排反应。在重排过程中,既有氢迁移,也会有烷基迁移,这取决于形成的碳正离子的稳定性。     

Diastereoselective rhodium(II)-catalyzed sulfonium ylide formation-[2,3]-sigmatropic rearrangement reaction of chiral non-racemic allylic sulfides

The tandem sulfonium ylide formation-[2,3]-sigmatropic rearrangement reaction of chiral non-racemic secondary allylic sulfides, (E)-9 and (Z)-10, is found to proceed with high diastereocontrol. The C-5 stereocenter bearing the sulfide group is essential for high diastereoselectivity in the reaction. Transition state conformers are proposed to explain the high diastereoselectivity in the formation of the diastereomeric products, 18a and 18b. The method is applied to the synthesis of (R)-4-(4-chlorophenyl)-2-butyrolactone. Modest enantioselectivity (63% ee) was achieved and this is attributed to partial racemization during the formation of the secondary allylic sulfide 22.     

Diastereoselective synthesis of carbapenams via Kinugasa reaction

A facile approach to carbapenams via Kinugasa reaction between terminal copper acetylides and nonracemic cyclic nitrones derived from malic and tartaric acid is reported. The stereochemical preferences observed in these reactions are explained. The reaction provides an entry to the carbapenams basic skeleton.     

Diastereoselective synthesis of delta-aminoacids through domino Ireland-Claisen rearrangement and Michael addition

A novel domino reaction--stereoselective Ireland-Claisen rearrangement and asymmetric Michael addition--is described. A protocol starting from Baylis-Hillman adducts 3a-f using chiral lithium amide affords optically active gamma-substituted delta-amino acids 4a-f with high diastereoselectivities and enantioselectivities. The acid can be isolated easily from large-scale reactions and transformed to 2,3-disubstituted piperidines 11 or 2-substituted nipecotic acid derivates 12.     

Diastereoselective formation of contiguous quaternary centers: the modified carroll rearrangement

A method is described for the diastereoselective formation of adjacent quaternary carbon atoms. The process involves a two-step transformation of an allylic β-ketoester into a single silyl keteneacetal which then undergoes a [3,3] sigmatropic rearrangement to generate the desired carbon-carbon bond in good yield and with excellent stereocontrol.     

Diastereoselective free radical halogenation,azidation, and rearrangement of beta-silyl Barton esters

[reaction: see text] Barton esters of beta-silylcarboxylic acids were decomposed by photolysis alone in organic solvents or in the presence of ethanesulfonyl azide or bromotrichloromethane. Products of the reaction, beta-silylthiopyridyl ethers, beta-silyl azides, or alkenes, were formed with significant control of stereochemistry.     

Investigation of a stereoselective co-mediated rearrangement reaction

A stereocontrolled approach to alpha-alkyl beta-alkynyl cyclohexanones is reported through a Lewis acid mediated rearrangement reaction of enol ethers bearing an Co-alkyne moiety. The reaction proceeds with high levels of stereoselectivity in the presence of Ti- and B-Lewis acids to provide a range of alpha,beta-disubstituted cyclohexanones in high yield although the products are prone to epimerization at the alpha-position in the presence of the B-promoter system. The potential for an enantioselective variant of this process is outlined, and a rationale for the observed stereochemical trends and detailed structural analyses of the ketone products are described.     

Diastereoselective synthesis of gamma-lactams by a one-pot, four-component reaction

A new one-pot, four-component reaction (4CR) between amines, maleic anhydrides, aldehydes, and thiols has been discovered to form tetra- and pentasubstituted gamma-lactams with high diastereoselectivity. Each component is independently variable and employed in equivalent stoichiometry, producing only water as a byproduct.     

Diastereoselective synthesis of β-aminocyclopentene sulfonic acid via hetero Diels-Alder reaction

A new cyclopentene GABA analogue was synthesized as a conformationally rigid analogue of the epilepsy drug vigabatrin. N-Sulfinyl dienophile Diels-Alder methodology, followed by alkaline hydrolysis of the corresponding dihydrothiazine oxide, oxidation and deprotection of the amino group gave cis-4-aminocyclopent-2-ene-1-sulfonic acid. The corresponding N,N-dimethylsulfinamide was also obtained.