Stereocontrolling Element Research Articles

ChemInform Abstract: Diastereo‐ and Enantiodifferentiation in Indium‐Promoted Allylations of 2,3‐Azetidinediones in Water. Definition of Long‐Range Stereocontrol Elements on π‐Facial Selectivity for β‐Lactam Synthesis.

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.

Diastereo- and Enantiodifferentiation in Indium-Promoted Allylations of 2,3-Azetidinediones in Water. Definition of Long-Range Stereocontrol Elements on π-Facial Selectivity for β-Lactam Synthesis

The stereochemical course of the reactions of N-benzyl-2,3-azetidinedione with six differently functionalized allylic bromides, as promoted by indium metal in 1:1 H2O−THF, were initially examined. ...

ChemInform Abstract: Applications of Chiral Sulfoxides as Stereocontrol Elements in Organic Synthesis

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.

Enantioselective synthesis of α-methyl carboxylic acids using a DiTOX chiral auxiliary

Five α-methyl carboxylic acids have been prepared with high e.e.s using 1,3-dithiane 1-oxide (DiTOX) units as the stereocontrolling elements and sources of chirality.

A modular approach to marine macrolide construction. 2. Concise stereocontrolled synthesis of the C17–C28 (CD) spiroacetal component

The CD spiroacetal ring system of altohyrtin A, which houses one-fifth of the stereogenic centers resident in the macrolide, has been synthesized through a combination of aldol condensations having different stereocontrol elements.

ChemInform Abstract: Hydrogen‐Bonding as a Stereocontrolling Element in Free‐Radical C‐ Allylation Reactions: Vicinal, Proximal, and Remote Asymmetric Induction in the Amino Acid Series.

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.

A Stereochemical Model for Merged 1,2- and 1,3-Asymmetric Induction in Diastereoselective Mukaiyama Aldol Addition Reactions and Related Processes

A systematic investigation of the direction and degree of stereoselectivity in aldol addition reactions is presented involving achiral unsubstituted metal enolate and enolsilane nucleophiles and chiral aldehydes. The BF3·OEt2 mediated Mukaiyama aldol reaction with α-unsubstituted, β-alkoxy aldehydes afforded good levels of 1,3-anti induction in the absence of internal aldehyde chelation. The level of 1,3-induction was found to be primarily dependent on the electrostatic nature of the aldehyde β-substituent. A revised model for 1,3-asymmetric induction is presented to account for these results based primarily on minimization of internal electrostatic and steric repulsion between the aldehyde carbonyl moiety and the β-substituents. A full conformational analysis, corroborated by semiempirical (AM1) calculations, is presented to support the proposed model. The merged impact of α and β aldehyde substituents was also systematically investigated, and an integrated 1,2- and 1,3-asymmetric induction model is proposed that incorporates the salient features of the Felkin−Anh and revised 1,3-model. In accordance with this integrated model, uniformly high levels of Felkin, 1,3-anti diastereofacial selectivity are observed in Mukaiyama aldol reactions with anti substituted α-methyl-β-alkoxy aldehydes, which contain stereocontrol elements that are in a stereoreinforcing relationship. In contrast, variable levels of aldehyde facial induction were observed in the corresponding reactions with syn substituted aldehyde substrates, which contain stereocontrol elements in a non-reinforcing relationship. The direction of aldehyde facial induction in Mukaiyama aldol additions to the syn substituted aldehydes was found to be primarily dependent on the size of the enolsilane, with the first known examples of anti-Felkin selective Mukaiyama aldol reactions observed under conditions known to preclude chelation for the addition of the enolsilane of acetone. We conclude that dominant 1,2-stereoinduction will be found in those reactions proceeding with the reactants in an antiperiplanar relationship, favored by sterically encumbered enolsilane substituents, while dominant 1,3-stereoinduction will be manifest from a synclinal transition state, preferred for less bulky enolsilane substituents. By inspection, the synclinal transition state may be destabilized by an increase in the steric bulk of the Lewis acid, and in accordance with this prediction the trityl perchlorate mediated enolsilane addition resulted in a dramatic reversal of facial selectivity relative to the BF3·OEt2 mediated reaction. These trends were also documented in the mechanistically related addition of allylstannanes to anti and syn disubstituted chiral aldehydes.

Hydrogen-Bonding as a Stereocontrolling Element in Free-Radical C-Allylation Reactions: Vicinal, Proximal, and Remote Asymmetric Induction in the Amino Acid Series

Hydrogen-Bonding as a Stereocontrolling Element in Free-Radical <i>C</i>-Allylation Reactions: Vicinal, Proximal, and Remote Asymmetric Induction in the Amino Acid Series

Remote Allylic Silyloxy Groups as Stereocontrol Elements in Intramolecular Oxymercurations of γ-Hydroxyalkenes

The diastereoselectivity in intramolecular oxymercurations of γ-hydroxyalkenes bearing a remote allylic oxy substituent has been investigated. It was found that the best selectivity was obtained by employing a combination of (Z)-alkene geometry and a tert-butyldiphenylsilyl protecting group attached to the remote allylic oxygen as in 4a−g. Cyclization, using mercuric acetate in dichloromethane, of all the (Z)-alkenols gave the syn diastereomer, 5a−g, as the major product. For example, cyclization of 4b gave syn diastereomer 5b and anti diastereomer 6b in a ratio of 7:1. It was found that this ratio could be improved by replacing dichloromethane with acetonitrile. Under these conditions the ratio of 5b to 6b increased to 19:1. Cyclization of (E)-alkene 9 gave very poor diastereoselection. These syn-selective intramolecular oxymercurations were exploited in enantioselective syntheses of two diastereomers of methyl nonactate.

Enantioselective synthesis of α-arylpropanoic acids

A range of (+)-α-arylpropanoic acids has been prepared in high enantiomeric excesses using 1,3-dithiane 1-oxide (DiTOX) units as the stereocontrolling elements and sources of chirality.

Asymmetric synthesis and absolute stereochemistry of cholesterol absorption inhibitor, SCH 48461

The first asymmetric synthesis of cholesterol absorption inhibitor, SCH 48461 is described. The compound was prepared from an asymmetric ester enolate-imine condensation using Oppolzer's chiral ester or the corresponding menthol ester as the stereocontrolling element. From analogy to literature examples, the absolute stereochemistry of the title compound was assigned to be 3 R, 4 S.

ChemInform Abstract: Chiral α,β‐Epoxy Group as a Stereocontrolling Element in the Reduction of N‐Metalloimines. A Short Synthesis of anti‐Epoxy Amines.

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.

Diastereoselective Addition of Nucleophiles to Carbonyl Compounds and Imines Controlled by α, β-Epoxy Group and Its Application in Organic Synthesis

Diastereoselective addition of nucleophiles to carbonyl and imine compounds with α- and/or β-substituents has been a valuable tool in the synthesis of complex molecules. Since optically active epoxides are easily accessible by Sharpless asymmetric epoxidation, the utiltiy of this group as a stereocontrolling element in such reactions is getting more and more highlighted recently. This account surveys diastereoselectivities in the nucleophilic additions to the C = X bonds found in i) α, β-epoxy aldehydes, ii) α, β-epoxy ketones, iii) α, β-epoxy imines, and iv) γ, δ-epoxy-α, β-unsaturated carbonyl compounds (conjugate addition) in this order and also presents some devices to achieve high selectivities as well as possible rationale of the stereochemical outcome in certain cases. Application of these reactions to the synthesis of biologically active compounds is also illustrated.

Chiral .alpha.,.beta.-epoxy group as a stereocontrolling element in the reduction of N-metalloimines. A short synthesis of anti-epoxy amines

Reduction of the α,β-epoxy N-metalloimines generated from the TBS ether of (2S,3S)-3-cyano-2,3-epoxy-1-propanol (1), Grignard reagents, and Me 3 SiCl with NaBH 4 afforded the TBS ethers of (2S,3S,4S)-4-amino-2,3-epoxy-1-alkanols 4 with diasteroselectivities of up to 95:5

ChemInform Abstract: Total Synthesis of Podophyllum Lignans: An Exploratory Study.

AbstractOn the basis of stereochemical considerations, the compound (IXb) seems to be an appropriate precursor for the podophyllotoxin system (I) because the cis‐substituted dioxane ring could be an essential stereocontrolling element.

Total synthesis of podophyllum lignans : an exploratory study

Approaches to podophyllotoxin 1c involving electrophilic ring closure as the crucial step have until now failed to produce the tetralin framework with the correct relative configuration. Stereochemical considerations allowed us to propose 18b as a precursor, in which the cis-substituted dioxane ring could be an essential stereocontrolling element. 18b was obtained with low selectivity via aldol condensation of 16 . The crucial ring closure failed because of the high reactivity under Lewis acid conditions of the oxygen at C-4, when incorporated in a 2-phenyl-1, 3-dioxane.

Ionophore synthesis. An enantioselective route to the left-wing of indanomycin (X- 14547A).

An enantioselective synthesis of the tetrahydropyran “left-wing” ofthe ionophore X-14547A is described, wherein stereoselective 1,2-carbonyl additions and an oxapyronone-to-dihydropyran enolate Claisen rearrangement are key stereocontrol elements.