Origin Of Diastereoselectivity Research Articles

On the Origin of Diastereoselectivity in [2 + 2 + 2] Cycloisomerization of Chiral Triynes: Controlling Helicity of Helicene-like Compounds by Thermodynamic Factors

Diastereoselective CoI-mediated [2 + 2 + 2] cycloisomerization of CH(3)O-substituted optically pure aromatic triynes to obtain nonracemic functionalized helicene-like compounds (comprising a penta-, hexa-, and heptacyclic helical scaffold) was studied. The stereochemical outcome of the reaction at 140 degrees C using CpCo(CO)(2) was controlled by thermodynamic factors yielding diastereomeric ratios up to 91:9. Using CpCo(ethylene)(2) at room temperature, a kinetic control took place leading to the loss of stereoselectivity. Barriers to epimerization for selected helicene-like compounds were measured indicating their lower configurational stability in comparison to the parent carbohelicenes. Free energy differences between corresponding pairs of diastereomers (calculated at the DFT B3LYP/TZV+P level) were in excellent agreement with the experimental data and allowed for the prediction of the stereochemical outcome of the reaction. An optically pure hexacyclic helicene-like alcohol was prepared on a multigram scale. Its X-ray structure confirmed the previous helicity assignments being based on (1)H-(1)H correlations in ROESY (1)H NMR spectra.

Origin of Diastereoselectivity in the Organolanthanide‐Mediated Intramolecular Hydroamination/Cyclisation of Aminodienes: A Computational Exploration of Constrained Geometry CGC–Ln Catalysts

The regulation of ring-substituent diastereoselectivity in the intramolecular hydroamination/cyclisation (IHC) of alpha-substituted aminodienes by constrained geometry CGC-lanthanide catalysts (CGC=[Me(2)Si(eta(5)-Me(4)C(5))(tBuN)](2-)) has been elucidated by means of a reliable DFT method. The first survey of relevant elementary steps for the 1-methyl-(4E,6)-heptadienylamine substrate (1) and the [{Me(2)Si(eta(5)-Me(4)C(5))(tBuN)}Sm{N(TMS)(2)}] starting material (2) identified the following general mechanistic aspects of Ln-catalysed aminodiene IHC. The substrate-adduct 3-S of the active CGC-Ln-amidodiene compound represents the catalyst's resting state, but the substrate-free form 3' with a chelating amidodiene functionality is the direct precursor for cyclisation. This step proceeds with almost complete regioselectivity through exocyclic ring closure by means of a frontal trajectory, giving rise to the CGC-Ln-azacycle intermediate 4. Subsequent protonolysis of 4 is turnover limiting, whilst the ring-substituent diastereoselectivity is dictated by exocyclic ring closure. Unfavourable close interatomic contacts between the substrate's alpha-substituent and the catalyst backbone have been shown to largely govern the trans/cis selectivity. Substituents of sufficient bulk in the alpha-position of the substrate have been identified as being vital for stereochemical induction. The present study has indicated that the diastereoselectivity of ring closure can be considerably modulated. The variation of the lanthanide's ionic radius and introduction of extra steric pressure at the substrate's alpha-position and/or the CGC N centre have been identified as effective handles for tuning the selectivity. The quantification of these factors reported herein represents the first step toward the rational design of improved CGC-Ln catalyst architectures and will thus aid this process.

Origin of Diastereoselectivity in the Synthesis of Chiral Bicyclic Lactams: π-Facial Selective Attack of Singlet Oxygen Induced by Hindered Internal Rotation

Previously reported experimental results indicate that photooxygenation of homochiral N-(hydroxyalkyl)-2-methylpyrroles with singlet oxygen yields trans-rather than cis-bicyclic lactams as the major product. In this study, the origin of selectivity in this reaction has been investigated with computational methods. Relative stabilities of homochiral N-(hydroxyalkyl)-2-methylpyrrole conformers and their effect on pi-facial selectivity of 1O2 were extensively studied. Stepwise and concerted reaction mechanisms, starting from the endoperoxide intermediates, were proposed and modeled in vacuum using the UB3LYP method with the 6-31+G** basis set. Solvent calculations were carried out in CH2Cl2, by means of the integral equation formalism-polarizable continuum model (IEF-PCM) at the UB3LYP/6-31+G** level of theory. Free energies of activation leading to both diastereomers were analyzed in an effort to explain the stereoselectivity and product distribution. Steric interactions among the pyrrole substituents were shown to lead to a rotational barrier higher than 10 kcal/mol. Hence, hindered internal rotation is suggested to cause one pyrrole conformer to be substantially overpopulated. This in turn has a major effect on pi-facial selectivity of 1O2, thereby favoring one endoperoxide over the other and leading to the diastereoselective synthesis of trans-pyrrolooxazolones. The importance of hindered internal rotors, for an accurate calculation of the frequency factors of a chemical reaction, has already been mentioned in the literature many times; however, in this work hindered internal rotors also seem to dictate the diastereoselective outcome of the reaction.

On the origins of diastereoselectivity in the alkylation of diketopiperazine enolates

High levels of diastereoselectivity are observed for benzylation of the lithium enolates of (S)-N,N′-bis-para-methoxybenzyl-3-iso-propyl-piperazine-2,5-dione, (S)-N(1)-para-methoxybenzyl-N(4)-methyl-3-iso-propyl-piperazine-2,5-dione and (S)-N(1)-methyl-N(4)-para-methoxybenzyl-3-iso-propyl-piperazine-2,5-dione. These data suggest that the high diastereofacial selectivity observed for alkylation of these diketopiperazine templates is mainly a consequence of the relay of stereochemical information from C(3) to C(6) via the influence of 1,2-torsional strain introduced by the N-alkyl substituents, rather than through minimisation of steric interactions alone.

Diastereoselection in the Formation of Spirocyclic Oxindoles by the Intramolecular Heck Reaction

Diastereoselective double Heck cyclizations of cyclohexene diamides 1 and 3 form contiguous quaternary stereocenters, with diastereoselection being controlled by the trans-diol protecting group. In this, the first in a series of two papers, the origin of diastereoselection in the first ring-closure step of these reactions is examined. Nine simplified analogues of 1 and 3 were synthesized and cyclized to discern what structural features are required to realize high diastereoselection in the first intramolecular Heck reaction. These studies show that high stereoselection (>20:1) does not arise from a single structural feature: it is seen only in substrates that contain both a trans-acetonide and a tertiary amide substituent at C2. Two subtle factors appear to be involved: (1) Avoidance of eclipsing interactions between the forming C-C bond and the pseudoaxial hydrogen atom at C6 and between the pseudoequatorial hydrogen atom at C6 and the carbonyl carbon of the forming spirooxindole. (2) The vinylic amide substituent that is not involved in the insertion event preferentially adopts a perpendicular conformation, placing the sterically bulky NR(2) over the alkene pi bond. syn-Pentane-like interactions between this substituent and the C3 of the cyclohexene are avoided in the favored insertion topography. These two effects, when combined, produce a highly diastereoselective process.

Origin of diastereoselection in the hydrosilylation of chiral N-acyliminium intermediates derived from pyroglutamic acid.

Origin of diastereoselection in the hydrosilylation of chiral N-acyliminium intermediates derived from pyroglutamic acid.

Origin of Diastereoselection in the Hydrosilylation of Chiral N‐Acyliminium Intermediates Derived from Pyroglutamic Acid

„Seitenwechsel“ für die Selektivität: Theoretischen Studien zufolge bestimmen sterische Abstoßung (oben) oder anziehende Wechselwirkungen (unten) zwischen unterschiedlichen Seitenketten und dem Silan-Nucleophil die Diastereoselektivität von Hydrosilylierungen chiraler cyclischer Iminium-Intermediate.

Origin of 1,3-induction in the addition of alkyl lithium to imines bearing an N-stereogenic center.

The origin of diastereoselectivity in the addition of alkyl lithium to chiral Schiff bases has been investigated experimentally and theoretically and the formation of the major diastereomer can be explained from the energy minimized structure of the Schiff base in which the phenyl group has been found to orient in such a manner that it posed lesser steric hindrance to the incoming nucleophile as compared to the alkyl group.

The origin of diastereoselectivity in cyclopropanation reactions of the iron carbene complex [(η5-C5H5)(CO)2FeCH[(η6-o-CH3OC6H4)Cr(CO)3]

Abstract The origin of diastereoselectivity in cyclopropanation reactions of the iron carbene complex [(η 5 -C 5 H 5 )(CO) 2 FeCH[(η 6 - o -CH 3 OC 6 H 4 )Cr(CO) 3 ]] + has been investigated. The chromium participation has been proved by the upfield shifts of both 1 H- and 13 C-NMR for C α  H and C α , which stabilized the iron carbene and may result in a late transition-state for the cyclopropanation reaction via tricarbonylchromium-complexed iron carbene. Hence, trans selectivity is expected. However, when using aromatic alkenes, a π stacking effect may exist during the transition-state, resulting in the cis selectivity for cyclopropanation.

Vinylogous Mannich reactions: some theoretical studies on the origins of diastereoselectivity.

[reaction: see text] Ab initio calculations at the RHF/3-21G level were used to investigate the limiting transition states in the addition of 2-methoxyfuran to a pyrrolinium ion. Four stationary points were found on the potential energy surface with relative energies of threo Diels-Alder, 0.0 kcal/mol; erythro open, 0.9 kcal/mol; erythro Diels-Alder, 1.3 kcal/mol; and threo open, 1.8 kcal/mol.

Origin of diastereoselectivity in the addition of allylsilane to chiral acyclic mixed acetals

Addition of allylsilane to chiral acyclic mixed acetals has been found to proceed via an SN1 mechanism and a model has been proposed to explain the observed diastereoselectivity.

ChemInform Abstract: Origin of Diastereoselectivity in the Thermal (4 + 2) Cycloadditions of Dienophiles Derived from Oppolzer′s Sultams: Steric vs. Stereoelectronic Influences.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Origin of diastereoselectivity in the thermal [4+2] cycloadditions of dienophiles derived from Oppolzer's sultams: Steric vs. Stereoelectronic Influences

AbstractComparative semi‐empirical PM3 and ab initio STO 3‐21G calculations on bornanesultam‐derived dienophiles containing the structural moiety SO2NC(O)X(α) = Y(β) suggest that, among the conformers of low energy, the thermodynamically less stable SO2/C(O)‐syn,C(O)/X=Y‐s‐cis conformation is also reactive in terms of LUMO level and atomic coefficients. Furthermore, the X(α), Y(β) LUMO atomic coefficients are nonequivalent with respect to both X(α)‐re and X(α)‐si faces, and thus have, depending on the conformation, a matching or mismatching stereoelectronic influence with the co‐operative steric effect. This dissymmetry is believed to result from the generalized anemone effect of the N lone pair, itself anomerically stabilized and directed, in the absence of crucial steric interactions, by the pseudo‐axial anti‐periplanar SO bond. Five N‐acyl‐substituted bornanesultams arc discussed ((–)‐1a: N‐acryloyl, XCH, YCH2; (–)‐1b; N‐crotonoyl, XCH, YCHMe; (–)‐1c: N‐N′‐fumaroyl, XCH, YCH(C(O)‐bornanesultam); 2a: N‐glyoxyloyl, XCH, YO; 2b: N‐acylnitroso, XN, YO). In this context, differences with toluenesultams 3 are pointed out. A previous report on N‐(acylnitroso)‐bornanesultam 2b is revisited, and the diastereoselectivity observed is shown to result from thermodynamic control.

Origins of diastereoselectivity in the alkylation of N-substituted lactams and amides derived from optically active aminoalcohols

The origins of diastereoselectivity in the alkylation of lactams 1a and 1b and amides 6a and 6b are discussed. A rigid intermediate in which the pyramidalized amide nitrogen chelated the alkoxide lithium cation is invoked. Further experiments conducted with different substrates are in agreement with the proposed model. Furthermore this model can explain the differences observed previously between ephedrine and pseudoephedrine amide alkylation.

Origin of diastereoselectivity in the nitrile oxide cycloadditions with Oppolzer's chiral sultams: coulombic interaction as the key role in diastereofacial differentiation

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrigin of diastereoselectivity in the nitrile oxide cycloadditions with Oppolzer's chiral sultams: coulombic interaction as the key role in diastereofacial differentiationKwang S. Kim, Byeang Hyean Kim, Won Min Park, Seung Joo Cho, and Byung Jin MhinCite this: J. Am. Chem. Soc. 1993, 115, 16, 7472–7477Publication Date (Print):August 1, 1993Publication History Published online1 May 2002Published inissue 1 August 1993https://doi.org/10.1021/ja00069a054RIGHTS & PERMISSIONSArticle Views208Altmetric-Citations34LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (650 KB) Get e-AlertsSupporting Info (3)»Supporting Information Supporting Information Get e-Alerts

On the origin of diastereoselection in the cyclization of enynes on low-valent zirconium centers. Substituent and torsional effects on annulation stereochemistry

On the origin of diastereoselection in the cyclization of enynes on low-valent zirconium centers. Substituent and torsional effects on annulation stereochemistry