DOCSLIB.ORG

Conformational Analysis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Conformational Analysis 1 Chemistry III (Organic): An Introduction to Reaction Stereoelectronics LECTURE 2 Stereoelectronics of Ground States – Conformational Analysis Alan C. Spivey [email protected] Nov 2015 2 Format & scope of lecture 2 • The conformation of hydrocarbons – Ethane & alkanes – Propene & alkenes • A1,2 and A1,3 strain – 1,3-Dienes & biaryls • The conformation of functional groups – Aldehydes & ketones – Esters & lactones • the ester anomeric effect • The conformation of functional groups – Amides – Acetals • the anomeric effect, Bohlmann IR bands – X-C-C-Y and R-X-Y-R’ systems • gauche effects 3 Saturated hydrocarbons - ethane • Ethane prefers to adopt a staggered rather than eclipsed conformation because: – 1) The eclipsed conformers are destabilised by steric interactions • i.e. by non-bonded, van der Waals repulsions between the atoms concerned – 2) The staggered conformers are stabilised by s → s* stereoelectronic interactions • i.e. in a staggered conformation all the bonds on adjacent carbons are anti periplanar to each other allowing six s → s* stabilising interactions s*C-H H H H H s*C-H H H H H H H sC-H = = E H H H H H H H H H H H H H H s ESTAB 6x sC-H ->s*C-H (app) C-H van der Waals repulsions are 'Cieplak' stereoelectronic stabilisation maximised when eclipsed (shown) is maximised when staggered (all six interacting bonds are anti periplanar) steric destabilisation of eclipsed conformations stereoelectronic stabilisation of staggered conformations – For theoretical discussions of the relative importance of these effects see • L. Goodman Nature 2001, 411, 539 (DOI) and 565 (DOI) • P.R. Schreiner Angew. Chem. Int. Ed. 2002, 41, 3579 (DOI) • F.M. Bickelhaupt Angew. Chem. Int. Ed. 2003, 42, 4183 (DOI) • F. Weinhold Angew. Chem. Int. Ed. 2003, 42, 4188 (DOI) – NB. Steric effects dominate for groups larger than hydrogen 4 Unsaturated hydrocarbons – propene • Propene prefers to adopt A1,3 eclipsed conformations rather than A1,2 eclipsed conformations – The barrier to rotation is 8.0 kJ/mol (cf. propane 14.8kJ/mol) H 3 H H H 2 H H H H Enthalpy diffference between conformers H 1 H 1 H° = +8.0 kJ/mol H H A1,3 eclipsed A1,2 eclipsed MAJOR 1,3 – The A eclipsed conformation allows for better overlap of the orbitals for stabilising sC-H → p*C=C hyperconjugation/s-conjugation • This better overlap is a consequence of the ~109° angle subtended by the ‘lobes’ of the p*C=C orbital relative to the C=C axis p*C=C p*C=C p*C=C H H H p*C=C sC-H H H H H s cf. H = E H C H = H C-H H H 2 H H2C H H H H ESTAB H sC-H A1,3 eclipsed conformation A1,2 eclipsed conformation H good orbital alignment poor orbital alignment NB. There are two concurrent interactions:on the top face (as indicated) and on the bottom face – NB. Steric effects dominate for groups larger than hydrogen... 5 Higher alkenes – A1,2 vs A1,3 strain • Steric interactions (i.e. van der Waals forces) dominate affairs when groups other than H are involved – A1,3 strain is the destabilising eclipsing interaction shown below: • As C=C double bonds are shorter than C-C single bonds, A1,3 strain in the illustrated conformation of 2-pentene is more destabilising than the syn-pentane interaction in the illustrated conformation of n-pentane H 3 H H H H H 2.47 Å 2.19 Å Me Me H 1 Me Me H Me Me Me Me 1,3 MAJOR A strain 3 1 Enthalpy diffference between conformers syn-pentane interaction A1,3 strain H° = +16.3 kJ/mol (+15.4 kJ/mol) (+16.3 kJ/mol) in n-pentane in 2-pentene – A1,2 strain is the destabilising eclipsing interaction shown below: • As the C-C-C angle at an sp3 carbon (~109°) is smaller than at an sp2 carbon (~120°), A1,2 strain in the illustrated conformation of 2-Me-but-1-ene is less destabilising than the eclipsing interaction in the illustarted conformation of n-butane A1,2 strain H H 2.76 Å 2 Me Me 2.54 Å H Me Me 120 Me 1 Me Me 109 Me H 2 1 MAJOR eclipsing interaction A1,2 strain Enthalpy diffference between conformers (+13.0 kJ/mol) (+12.6 kJ/mol) H° = +12.6 kJ/mol n-butane 2-Me-but-1-ene – For a given pair of groups (e.g. Me ↔ Me, above), A1,3 strain is more destabilising than A1,2 strain. The lowest energy conformation adopted by complex alkenes is that in which both A1,2 & A1,3 strains are minimised 6 Unsaturated hydrocarbons – 1,3-dienes • 1,3-Dienes prefer to adopt s-trans conformations in which both double bonds are co-planar – e.g. butadiene: H H H H H H H H H H H Enthalpy diffference between conformers Steric clash H° = +25 kJ/mol H s-trans s-cis MAJOR – Co-planarity of the p bonds allows for optimal overlap of the orbitals for pC=C → p*C=C resonance stabilisation pC=C p* p -> p* (pp) C=C Maximum p -> p* stabilisation C=C C=C E for periplanar alkenes (i.e. best overlap) p*C=C ESTAB pC=C – The s-trans conformation is preferred over the s-cis conformation because it suffers less A1,3 strain 7 Unsaturated hydrocarbons - biaryls • Biaryls prefer to adopt non-planar conformations in which the dihedral angle is ~45° R' R R' = R'' R Lowest energy conformation has dihedral angle ca. 45° R'' R''' R''' – This is a compromise between: • Stabilising pC=C → p*C=C resonance when coplanar • Destabilising steric interactions between adjacent ortho aromatic substituents when coplanar Destabilising A1,3 strain ( = 0°, 180°, 360°) typical for >100 R,R',R'',R''' alkyl H in Stabilising pC=C -> p*C=C resonance ( = 90°, 270°) kJ/mol 0 0 90 180 270 360 in degrees – If at least three ortho substituents are large then the co-operative steric interactions restrict C-C bond rotation to such an extent that the two conformers become configurationally stable and, provided the groups are different, can be isolated as enantiomers known as atropisomers 8 Functional groups – aldehydes & ketones • Alkyl aldehydes & ketones prefer to adopt A1,3 eclipsed conformations H H H H O O H H H H A1,3 eclipsed A1,2 eclipsed MAJOR 1,3 – As for allylic systems, A eclipsed conformations allow stabilising sC-H/C → p*C=O hyperconjugation/ s-conjugation • These interactions are more significant than the corresponding interactions in an allylic system because the p*C=O orbital is a better acceptor (i.e. is lower in energy) than a p*C=C orbital • These interactions also account for the greater stability of ketones relative to aldehydes (i.e. Deslongchamps theory: more interactions for the ketone) p*C=O p* H C=O H H sC-H p* O C sC-H cf. O C C=O H H E H H E 1,3 s STAB A eclipsed A1,2 eclipsed C-H good orbital alignment poor orbital alignment NB. of course there are two identical interactions: on the top and bottom faces – Moreover, A1,3 strain is less significant in these compounds relative to allylic compounds as the sp2 hybrid lone pairs on the carbonyl oxygen are ‘small’ relative to any substituent on an alkene 9 Functional groups - esters • Esters prefer to adopt s-cis conformations in which all atoms of the group are co-planar H° ~25kJ/mol Me # H# ~50 kJ/mol H O Me O O H Me Me O s-trans H° s-cis s-trans s-cis MAJOR – Co-planarity is stabilised by nOp → p*C=O resonance s bond s bond R' n -> p* (pp) R' n -> p* (pp) C O R' C O R' p*C=O O O E p* p* O C=O O R O C=O R O R ESTAB R nOp nOp nOp s-cis s-trans – Because the p-orbital on oxygen is symmetrical resonance does not favour either relative to the other – However, there is a relatively strong enthalpic preference for the s-cis conformer over the s-trans one (H° ~25kJmol-1 cf. ~10kJmol-1 for amides) although the barrier to rotation about the acyl oxygen bond (i.e. interconversion) is relatively low (H# ~50kJmol-1 cf. ~85kJmol-1 for amides) Functional groups – esters cont. 10 • There are three factors which favour the s-cis over the s-trans conformer: – There is a nOsp2 → s*C-O anomeric effect which stabilises the s-cis form p bond s* R' C-O n -> s* (app) s*C-O C O R' E O O O R ESTAB nOSp2 nOSp2 R – There is significant A1,2 strain in the s-trans form (the sp2 hybrid lone pair on the carbonyl oxygen is ‘small’ relative to a substituent bonded to the acyl carbon atom) A1,2 strain R' O R' O O R R O s-cis s-trans – The s-cis form has a significantly smaller overall dipole moment relative to the s-trans form • There is a general preference for conformers with minimum overall dipole (minimum overall charge separation) R' s-cis O R' s-trans bond dipole bond dipole O O moments moments NB. R R O antiparrallel ~parrallel 11 Evidence for the ester anomeric effect • Fluorocarbonates prefer to adopt an s-trans conformation: F O F O NB. the cis and trans designations O R O here are relative to the carbonyl R group and not strictly according to s-cis s-trans CIP rules (where F>O) MAJOR – Here, the s* orbital of the C-F bond is a better acceptor than the s* orbital of the C-O bond (i.e.
Load more

Recommended publications
  • Stereoelectronic Effects in Nucleosides and Nucleotides and Their Structural Implications
    Stereoelectronic Effects in Nucleosides and Nucleotides and their Structural Implications (including Appendix on literature up to 2005) Christophe Thibaudeau, Parag Acharya and Jyoti Chattopadhyaya* *To whom correspondence should be addressed. E-mail: [email protected] F +4618554495 T +46184714577 www.boc.uu.se Department of Bioorganic Chemistry Biomedical Center, Uppsala University, Sweden 2 Christophe Thibaudeau, Parag Acharya and Jyoti Chattopadhyaya* Dept of Bioorganic Chemistry Uppsala University Biomedical Center, Box 581 S-751 23 Uppsala Dr C. Thibaudeau has completed his Ph.D in Feb, 1999 at the Dept of Bioorganic Chemistry under the supervision of Prof J. Chattopadhyaya Dr P. Acharya has completed his Ph.D in Dec, 2003 at the Dept of Bioorganic Chemistry under the supervision of Prof J. Chattopadhyaya Dr J. Chattopadhyaya is professor of Bioorganic Chemistry at the Uppsala University Use the following for citation in your reference: Uppsala University Press First Edition: 1999; Second Edition, 2005 Copyright © May, 1999 by J. Chattopadhyaya, C. Thibaudeau and P. Acharaya ISBN 91-506-1351-0 pp 166 Chattopadhyaya et al, "Stereoelectronic Effects in Nucleosides & Nucleotides and their Structural Implications", Dept of Bioorganic Chemistry, Box 581, Uppsala University, S-75123 Uppsala, Sweden, Ver 160205 [email protected] 3 The intrinsic flexibility of pentoses in natural PREFACE nucleosides and nucleotides, owing to their lower energy barrier for interconversions compared to the The three essential components of DNA and RNA are hexopyranoses, is dictated by the energetics of the aglycone, the pentofuranose sugar in β-D stereochemistry stereoelectronic effects, which simply can be tuned and the phosphodiester. The phosphates at the backbone and modulated by choice of substituents and their makes DNA/RNA to behave as polyelectrolyte, the pentose ionization state as well as by their complexation with sugar gives the intrinsic flexibility with relatively low energy potential ligands present in the medium.
    [Show full text]
  • Stereoelectronic Effects on Stability and Reactivity of Organic Molecules
    Stereoelectronic effects on stability and reactivity of organic molecules: from control of molecular conformations to faster cycloadditions and cyclizations Igor Alabugin, Florida State University Зимняя конференция молодых ученых по органической химии, January 20, 2015, Krasnovidovo Importance of delocalization This image cannot currently be displayed. Introduction What is the most stable structure/geometry in the following pairs? Take a second and make your guess: Is there a common theme? Am I going mad? From Alabugin, “Stereoelectronic effects” This image cannot currently be displayed. There is a common underlying effect It can be expanded to many common functional groups. See if you can spot it Good News: There are preferred geometries for interactions between molecules, or between parts of a molecule. These “rules of engagement” are called stereoelectronic effects. From Alabugin, “Stereoelectronic effects” This image cannot currently be displayed. Stereoelectronic effects Definition: Stereoelectronic effects – interactions of electronic orbitals in three dimensions. The typical stereoelectronic effect involves an electronic interaction which stabilizes a particular conformation or transition state and is fully expressed only when the correct geometry is achieved. Caveat: “stereoelectronic” is not the same as “steric + electronic”! Stereoelectronic effects are always stabilizing and reflect increased delocalization at favorable conformations. From Alabugin, “Stereoelectronic effects” This image cannot currently be displayed. Types of interactions Types of orbitals Directionality of electron transfer Types of resonance: negative, positive and neutral conjugation and hyperconjugation Donation of electron density from filled ‐orbitals into *‐orbitals or p‐type cationic centers is referred to as positive hyperconjugation. The interactions between filled or p‐orbitals and adjacent antibonding *‐orbitals are called negative hyperconjugation.
    [Show full text]
  • Hyperconjugation Article Type
    Article Title: Hyperconjugation Article type: Advanced review Authors: Igor V Alabugin* 0000-0001-9289-3819, Florida State University, [email protected], this author declares no conflicts of interest Gabriel dos Passos Gomes 0000-0002-8235-5969, Florida State University, [email protected], this author declares no conflicts of interest Miguel A Abdo 0000-0002-2009-6340, Florida State University, [email protected], this author declares no conflicts of interest Keywords Bond theory, Hyperconjugation, Stereoelectronic effects, Delocalization, Orbital Graphical abstract This review outlines the role of hyperconjugative interactions in the structure and reactivity of organic molecules. After defining the common hyperconjugative patterns, we discuss the main factors controlling the magnitude of hyperconjugative effects, including orbital symmetry, energy gap, electronegativity, and polarizability. The danger of underestimating the contribution of hyperconjugative interactions are illustrated by a number of spectroscopic, conformational, and structural effects. The stereoelectronic nature of hyperconjugation offers useful ways for control of molecular stability and reactivity. New manifestations of hyperconjugative effects continue to be uncovered by theory and experiments. 1 Hyperconjugation, conjugation and σ-conjugation: The classic picture of covalent chemical bonding starts by creating the framework of two- center/two-electron bonds. These bonds are formed by sharing of electron pairs which is a quantum mechanical phenomenon based
    [Show full text]
  • The Orbital Interaction Component of Conformational Effects
    THE ORBITAL INTERACTION COMPONENT OF CONFORMATIONAL EFFECTS Ronald Y.N. Leung B.Sc., University of Ulster, 1982. THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in the Department of Chemistry @ Ronald Y.N. Leung 1991 SIMON FRASER UNIVERSITY February 1991 All rights reserved. This work may not be reproduced in whole or in part, by photocopy or other means, without permission of the author. APPROVAL Name: Ronald Y. N. Leung Degree: Doctor of Philosophy Title of thesis: The Orbital Interaction Component of Conformational Effects Examining Committee: Chairman : Dr. P. W. Percival Dr. B. M. pinto Senior Supervisor Dr. Y. L. &h&\ Committee Member Dr. A. S. Tracey Committee Member Dr.'s. Wolfe Internal Examiner Dr. A. Rauk External Examiner Department of Chemistry University of Calgary Date of Approval: WQ~15 , 71 PARTIAL COPYRIGHT LICENSE I hereby grant to Simon Fraser University the right to lend my thesis, proJect or extended essay (the title of which is shown below) to users of the Simon Fraser University Library, and to make partial or single copies only for such users or in response to a request from the library of any other university, or other educational Institution, on its own behalf or for one of Its users. I further agree that permission for multiple copying of this work for scholarly purposes may be granted by me or the Dean of Graduate Studies. It is understood that copying or publlcatlon of this work for financial gain shal I not be a1 lowed without my written permission. Title of Thes i s/Project/Extended Essay d IHE OR~IT&L INTERACT~ON COW pofd~NT OF Author: Q.ao, 9) (date) ABSTRACT A combination of experimental and computational approaches has provided details for the analysis of the steric, electrostatic and orbital interaction components of conformational effects operating in substituted heterocycles containing the 0-C-N, S-C-N, 0-C-0, S-C-0, 0-C-C-N, S-C-C-N, 0-C-C-0 and S-C-C-0 fragments.
    [Show full text]
  • The C–F Bond As a Conformational Tool in Organic and Biological Chemistry
    The C–F bond as a conformational tool in organic and biological chemistry Luke Hunter Review Open Access Address: Beilstein Journal of Organic Chemistry 2010, 6, No. 38. School of Chemistry, The University of Sydney, NSW 2006, Australia doi:10.3762/bjoc.6.38 Email: Received: 12 January 2010 Luke Hunter - [email protected] Accepted: 15 March 2010 Published: 20 April 2010 Keywords: Guest Editor: D. O’Hagan conformation; functional molecules; organofluorine chemistry; stereochemistry; stereoelectronic effects © 2010 Hunter; licensee Beilstein-Institut. License and terms: see end of document. Abstract Organofluorine compounds are widely used in many different applications, ranging from pharmaceuticals and agrochemicals to advanced materials and polymers. It has been recognised for many years that fluorine substitution can confer useful molecular prop- erties such as enhanced stability and hydrophobicity. Another impact of fluorine substitution is to influence the conformations of organic molecules. The stereoselective introduction of fluorine atoms can therefore be exploited as a conformational tool for the synthesis of shape-controlled functional molecules. This review will begin by describing some general aspects of the C–F bond and the various conformational effects associated with C–F bonds (i.e. dipole–dipole interactions, charge–dipole interactions and hyper- conjugation). Examples of functional molecules that exploit these conformational effects will then be presented, drawing from a diverse range of molecules including pharmaceuticals, organocatalysts, liquid crystals and peptides. Review General aspects of the C–F bond Fluorine is a small atom, with an atomic radius intermediate charges attract each other. Hence, the C–F bond has significant between that of hydrogen and oxygen (Table 1).
    [Show full text]
  • Steric Vs Electronic Effects: a New Look Into Stability of Diastereomers, Conformers and Constitutional Isomers
    Communication Steric vs Electronic Effects: A New Look Into Stability of Diastereomers, Conformers and Constitutional Isomers Sopanant Datta and Taweetham Limpanuparb * Science Division, Mahidol University International College, Mahidol University, 999 Phutthamonthon 4 Rd., Salaya, Phutthamonthon, Nakhon Pathom 73170, Thailand; [email protected] (S.D.) * Correspondence: [email protected] Abstract: A quantum chemical investigation of the stability of compounds with identical formulas was carried out on 23 classes of halogenated compounds made of H, F, Cl, Br, I, C, N, P, O and S atoms. All possible structures were generated by combinatorial approach and studied by statistical methods. The prevalence of formula in which its Z configuration, gauche conformation and meta isomer are the most stable forms is calculated and discussed. Quantitative and qualitative models to explain the stability of the 23 classes of halogenated compounds were also proposed. Keywords: Steric effect; electronic effect; cis effect; gauche effect 1. Introduction Steric effects, non-bonded interactions leading to avoidance of spatial congestion of atoms or groups, are often the central theme in the discussion of stability of diastereomers, conformers and constitutional isomers. Reasonings based on steric effects are relatively intuitive and give rise to a generally accepted rule of thumb that E configuration, anti conformer and para isomer in diastereomers, conformational and constitutional isomers, Citation: Datta, S.; Limpanuparb, T. respectively, should be the most stable forms. Steric vs Electronic Effects: A New Many findings in contrary to steric predictions exist in the literature. Table 1 shows Look Into Stability of Diastereomers, a comprehensive review of experimental and theoretical evidence of the Z configuration, Conformers and Constitutional Iso- gauche conformer and meta isomer being the most stable forms.
    [Show full text]
  • The Anomeric Effect Paul Krawczuk
    Wednesday, November 9, 2005 Baran Group Meeting The Anomeric Effect Paul Krawczuk Further Reading: G.R.J. Thatcher (ed.), The Anomeric Effect and Related Stereolectronic Effects. ACS Anomeric Effect Defined (IUPAC): Symposium Series #539, 1993. Review: Juaristi, E., Cuevas, G., Tetrahedron, 1992, 48(24), 5019-5087. Originally defined as the thermodynamic preference for polar groups bonded to C-1 (the anomeric carbon of a glycopyranosyl derivative) to take up an Historical Aspects of the Anomeric Effect axial position. First observed in 1955 by J.T. Edward and in 1958 by R.U. Lemieux. O O Both were studying carbohydrate chemistry and noticed a preference for ~1.5 kcal alkoxy and acetyl groups to reside in the axial position. Edward proposed OR that the lone pairs on the ring oxygen were contributing to the effect. OR -OR has an axial preferecne in a C1 substituted tetrahydropyran alkyl substituted cyclohexanes prefer equitorial orientation over axial R This effect is now considered to be a special case of a general preference R (the generalized anomeric effect) for gauche conformations about the bond C–Y in the system X–C–Y–C where X and Y are heteroatoms O having nonbonding electron pairs, commonly at least one of which alkyl substituted tetrahydropyrans O show this same preference is nitrogen, oxygen, sulfur or fluorine. R Y Y R X Electronegativites X H OH H OH of Relavant Atoms the anomeric carbon of the most H O H O abundant natural sugar, HO HO C 2.5 HO H HO OH S 2.5 D-glucopyranose, also prefers an H H OH OH R X R H N 3.0 equtorial orientation.
    [Show full text]