Diastereo- and regioselectivity in Diels-Alder reaction of [1,4,2]diazaphospholo[4,5-a]pyridines

[1,4,2]Diazaphospholo[4,5-a]pyridines undergo diastereoselective Diels-Alder reaction at the >CP- functionality with 2,3-dimethylbutadiene and isoprene in the presence of sulfur or selenium. The reaction with isoprene occurs regioselectively. On carrying out the reaction with diene in presence of methyl iodide, the initially formed [2+4] cycloadduct is methylated regioselectively at the σ²,λ³-nitrogen. The results of the DFT calculations of the Diels-Alder reaction with isoprene are in accord with the observed regioselectivity. The relative stabilities of the two transition structures have been explained on the basis of NBO analysis.     

A highly regio- and chemoselective synthesis of vicinal bromohydrins by ring opening of terminal epoxides with dibromoborane-dimethyl sulfide

Dibromoborane-dimethyl sulfide (BHBr₂-SMe₂) displays high degrees of chemo- and regioselectivity during the brominative cleavage of the epoxy group into vicinal bromohydrins in the presence of alkene, alkyne, allene, ether, acetal and acetonide, besides its hydroborating ability. Several reducible functional groups, such as chloride, aldehyde, ketone, azide, ester, nitrile and tert-amino ester, have been successfully accommodated during the epoxide opening process.     

Theoretical studies on selectivities in the Staudinger reaction of vicinal diimines and ketenes

The selectivities,including peri-,regio-,and diastereoselectivities,in the Staudinger reaction involving vicinal diimines and ketenes were investigated theoretically via the density functional theory(DFT) calculation.The results indicate that vicinal diimines prefer stepwise [2+2] cycloaddition rather than [2+4] cycloaddition to generate cis-4-imino-β-lactams.The diimines attack the less sterically hindered exo-side of ketenes to generate zwitterionic intermediates,which directly undergo a conrotatory ring closure to produce cis-4-imino-β-lactams whatever diimines with less or more bulky N-substituents.For unsymmetric vicinal ketoaldehyde-derived diimines,their ketimines attack the exo-side of ketenes and undergo a conrotatory ring closure to produce cis-4-aldimino-β-lactams due to less steric effect.The current theoretical studies provide very important information for in-depth understanding of the selective formation of mono-cis-β-lactams from vicinal diimines and ketenes.     

Palladium-catalyzed regio- and diastereo-selective allylic alkylation using 2-(diphenylphosphino)benzoic acid: construction of vicinal quaternary and tertiary carbon centers

The palladium-catalyzed regio- and diastereo-selective allylic alkylation of allyl acetates with carbon nucleophiles occurred. The stereochemistry was highly controlled by the palladium catalyst with 2-(diphenylphosphino)benzoic acid as the ligand, and vicinal quaternary and tertiary carbon centers were constructed.     

Diastereoselectivity in the Staudinger reaction: a useful probe for investigation of nonthermal microwave effects

The effect of microwave irradiation on the selectivity, especially stereoselectivity, is one of the most important issues in microwave-assisted organic reactions. The diastereoselectivity in Staudinger reactions involving the representative ketenes and the corresponding matched imines has been used as a probe to investigate carefully the existence of the specific nonthermal microwave effects. The results indicate that the microwave irradiation-controlled stereoselectivity in the Staudinger reaction is in fact the contribution of temperature. No specific nonthermal microwave effect was found in the Staudinger reaction.     

α-Amino acids as acid components in the Passerini reaction: influence of N-protection on the yield and stereoselectivity

The Passerini reaction offers an easy access to depsipeptides, when both acid and isocyanide are derived from α-amino acids. However, racemisation of isocyanides derived from α-amino acid esters severely limits their use in the Passerini reaction. In order to overcome this limitation, a study on the influence of the α-amino acid N-protecting group on the yield and diastereoisomeric ratio of the product of the Passerini reaction was performed. Six different protecting groups were tested. Their influence turns out to be crucial and is not constant when the amino acid is changed. After optimisation, the Passerini reaction products with cyclohexanone as the carbonyl component were obtained with 99% yield and >98% de.     

Elucidating the Mechanism and Chemoselectivity in the PBu3-Catalyzed Rauhut-Currier Reaction of Chalcone with Ethyl Acrylate

Disclosing the chemoselectivity and regioselectivity of phosphine-catalyzed Rauhut-Currier (R−C) reaction remains a challenge. Here, a comprehensive study on the possible mechanisms and origins of the chemoselectivity and regioselectivity of PBu₃-catalyzed R−C reactions between ethyl acrylate and chalcone is performed by DFT. Both cross and homo R−C reactions are investigated and compared. The computational results show that the cross R−C reaction is energetically favorable than the homo R−C reaction, with head-to-tail product being generated preferentially. Moreover, the C−C bond formation process is identified to be the regioselectivity- and chemoselectivity-determining step. The CDFT and Parr function analyses are successfully used to predict the origins of chemoselectivity and regioselectivity, respectively. This work would provide a valuable case for exploring the origins of the chemoselectivity and regioselectivity of the phosphine catalyzed reactions, which should be helpful to understand and control the selectivities by rational design.     

Regiochemical control in the amination reaction of phenanthridine-7,10-quinones

The reaction of substituted phenanthridine-7,10-quinones with amines to construct novel aminophenanthridinequinone derivatives as antitumor agents is described. The regiochemistry of the amination reaction is discussed in terms of inductive and steric effects of remote substituents to the quinone ring, which control the direction of the conjugate addition of the amines across the quinone double bond. Evidences on the significant in vitro antitumor activities of some of the obtained aminoquinones, are reported.     

Effect of the heteroatomic substituent on the pi-facial diastereoselectivity in Lewis acid catalyzed carbonyl ene reaction: A theoretical study

Quantum chemical investigation on the optimized transition structures of intermolecular ene reaction containing various heteroatomic substituents at the -carbon atom reveal that, the electrostatic effect produced by the ene moiety plays a crucial role in controlling the conformation of the transition structure. The stereoselectivity calculated from the proposed model agreed nicely with the reported experimental results.     

One-step synthesis of alpha-pyrones from acyl chlorides by the Stille reaction

Palladium-catalyzed stereoselective annulation of a functional vinylstannane by acyl chlorides gives the corresponding alpha-pyran-2-ones in good yields. This annulation most probably proceeds through a Stille reaction/cyclization sequence.     

Chemo- and regioselectivity in the reactions of polyfunctional pyrroles

The chemo- and regioselectivity of the reduction, oxidation and Wittig reaction of polyfunctional pyrroles, containing a variety of reactive centres was investigated. The reaction of 3,5-dichloropyrrole-2,4-dicarboxaldehydes with potassium permanganate leads to regioselective oxidation of the 2-formyl group, while the Wittig reaction with 1 equiv of a triphenylphosphorane produced the 2-alkenyl substituted pyrroles.     

Assessment of the regioselectivity in the condensation reaction of unsymmetrical o-phthaldialdehydes with alanine

One approach for the synthesis of isoindolinones, a privileged bioactive heterocyclic core structure, involves a condensation reaction of o-phthaldialdehydes with a suitable nitrogen-containing nucleophile. This fascinating reaction is revisited here in the context of the use of o-phthaldialdehydes that contain additional substituents in the aromatic ring leading to a detailed analysis of the regioselectivity of the reaction. Eleven monosubstituted o-phthaldialdehydes were synthesised and reacted with alanine. The regioselectivity observed across the eleven substrates led to the design of a disubstituted substrate that reacted with very high control. A gram-scale reaction followed by esterification gave one major regioisomer in high yield. In addition, the regioselectivity observed on reaction of two novel monodeuterated substrates led to an increased mechanistic understanding.     

Efficient and selective solid-phase synthesis of trans 3-alkyl β-lactams from nonactivated acid chlorides

An efficient and stereoselective procedure for a rapid access to diverse trans 3-alkyl β-lactams by solid-phase methodology is described.     

The catalytic tandem oxidation/benzilic ester rearrangement (BER): insights into reaction mechanism and stereoselectivity

This Letter describes an expeditious regiospecific and stereoselective approach to tertiary α-hydroxyesters via a simple one pot tandem catalytic oxidation/benzilic ester rearrangement of acyclic α-hydroxyketone substrates. Mechanistic studies confirming the regioselective nature of this reaction are discussed, including some insights into the nature of the stereoselectivity encountered in this reaction.     

Iridium-Catalyzed Chemo-, Diastereo-, and Enantioselective Allyl-Allyl Coupling: Accessing All Four Stereoisomers of (E)-1-Boryl-Substituted 1,5-Dienes by Chirality Pairing

Here, we report a highly chemo-, diastereo-, and enantioselective allyl-allyl coupling between branched allyl alcohols and α-silyl-substituted allylboronate esters, catalyzed by a chiral iridium complex. The α-silyl-substituted allylboronate esters can be chemoselectively coupled with allyl electrophiles, affording a diverse set of enantioenriched (E)-1-boryl-substituted 1,5-dienes in good yields, with excellent stereoselectivity. By permuting the chiral iridium catalysts and the substrates, we efficiently and selectively obtained all four stereoisomers bearing two consecutive chiral centers. Mechanistic studies via density functional theory calculations revealed the origins of the diastereo- and chemoselectivities, indicating the pivotal roles of the steric interaction, the β-silicon effect, and a rapid desilylation process. Additional synthetic modifications for preparing a variety of enantioenriched compounds containing contiguous chiral centers are also included.     

Unexpected 1,2 syn diastereoselectivity in the three-component ‘aza Sakurai-Hosomi’ reaction

The three-component ‘aza Sakurai-Hosomi’ reaction performed on (±) O-protected mandelic aldehydes provided the unexpected syn hydroxy homoallylamines 2 and 2d as the major adducts. An intramolecular chelated transition state via a hydrogen bond is proposed to explain this 1,2 syn diastereoselectivity.     

γ-Heteroatom directed stereocontrolled Staudinger cycloaddition reaction of vinylketenes and imines

Vinylketenes possessing a γ-heteroatom, on Staudinger cycloaddition reaction with imines gave trans-3-vinyl-β-lactams in very good yields. The vinyl side chain stereoselectively adopts the Z-configuration in the transition state to stabilize the vinylketene and produces, exclusively, trans-3-vinyl-β-lactams.     

Indium-mediated formation of propargyl ketones from aldehydes or acyl chlorides

Propargyl ketones were prepared from aldehydes via an indium-mediated alkynylation reaction followed by an indium-mediated Oppenauer oxidation. They were also obtained via an indium-mediated alkynylation of the relevant acyl chlorides.     

Observation of 1,3-diketones formation in the reaction of bulky acyl chlorides with methyllithium

The formation of 1,3-diketones was observed in the reactions of bulky acyl chlorides with methyllithium. The reaction products depend on the steric hindrance around the carbonyl group of the acyl chloride and the electronic effect of the group(s) linked to the carbonyl. When the steric hindrance around the carbonyl group of the acyl chloride is big enough, the 1,3-diketone is the only product. In the case of the moderate hindrance around the carbonyl group of the acyl chloride, a moderate yield of 1,3-diketone is obtained and some tertiary alcohol is generated. When there is no steric hindrance around the carbonyl group of the acyl chloride, the tertiary alcohol is the only product. When the steric hindrance around the carbonyl group is moderate and an electron-donating group is connected to the carbonyl of the acyl chloride, all three products--ketone, 1,3-diketone and tertiary alcohol--can be isolated from the reaction mixture after long reaction times.