Chapter 3 Stereochemistry and Conformational Analysis 1 Conformational

Chapter 3 Stereochemistry and Conformational Analysis 1. Conformational analysis 2. Strain 3. A brief review on stereochemistry Suggested Readings: • • • Please refresh your 1 st year organic chemistry on this topic. E. V. Anslyn and D. A. Dougherty “Modern Physical Organic Chemistry”, University Science Books, 2006, Chapters 2 and 8. E. L. Eliel and S. H. Wilen “Stereochemistry of Organic Compounds”, Wiley, 1994, Chapters 10 and 11.

This symbol (☮) was adopted as its badge by the Campaign for Nuclear Disarmament in Britain, and originally, its use was confined to supporters of that organization. It was later generalised to become an icon of the 1960 s anti-war movement, and was also adopted by the counterculture of the time. It was designed and completed February 21, 1958 by Gerald Holtom, a commercial designer and artist in Britain.

F-Gauche effect Wiberg bent bond model ACR 1996, 29, 229.

Gauche interaction 0. 9 kcal

Fluorine atom is small !! Schlosser, M. Tetrahedron 1978, 34, 3.

Bond lengths (pm)

Strain - Bond length strain (normal C-C bond length ~ 1. 54 A) 1. 64 -5 A 1. 38 A JACS 1988, 110, 6670. 1. 47 A 1. 463 A 1. 436 A ACIE 2005, 44, 5821. JACS 1999, 121, 4111. - Angle strain-small rings and medium rings For cyclopropane, reduction of “bond angles from ideal 109. 5 o to 60 o, 27. 5 Kcal/mol of strain energy. Medium rings (8 -11) Bond angles enlarged from ideal 109. 5 o to 115 -120 o to reduce Transannular interactions.

Strain (continued) - Torsional strain Deviation from ideal dihedral angle of 60 o and approach an eclipsing interaction. 5 -, 6 - and 7 -membered rings are largely unstrained and the strain that is present is largely torsional strain. - Nonbonding interactions Analogous to 1, 3 -diaxial interactions in cyclohexanes, but can be 1, 3 -, 1, 4 -, or 1, 5 -… This kind of interaction is commonly seen in medium rings (8 -11). Large rings (12 -membered and up) have little or no strain.

Group increments for heat of formation • • CH 3 -10. 05 Kcal/mol CH 2 -5. 13 Kcal/mol CH -2. 16 Kcal/mol C -0. 30 Kcal/mol

Strained Hydrocarbons: What is the limit? Exotic polyhedra: The Five Platonic or Cosmic Solids (Plato 350 BC) Tetrahedron (fire) Cube (earth) There are two more: icosahedron (water) Dodecahedron (“ether”) and octahedron (air) Can we make the corresponding hydrocarbon frames (CH)n ?

Maier, 1978, tetra-t-Butetrahedrane. Substituted C 4 H 4 m. p. 135°C ! Strain: 130 kcal mol-1 m. p. 202°C Maier, Sekiguchi, 2002, tetrakis(trimethylsilyl)tetrahedrane. Eaton, 1964, cubane, C 8 H 8 m. p. 126°C Strain: 166 kcal mol-1 m. p. 430°C ! Strain: 60 kcal mol-1 Paquette, 1982, dodecahedrane, C 20 H 20, 12 faces

Octanitrocubane: a New Explosive and Rocket Fuel Eaton, Adv. Mat. , 2000.

Stereochemistry-a brief review • Absolute configuration Fischer’s Definition on D and L CPI Notation • Enantiomers vs diastereomers • Meso form vs dl form • Enantiotopic vs diastereotopic

1 H-1 H Couplings-A Review • Any two nuclei with nuclear spin spaced by no more than three covalent bonds may couple. • Coupling constants between two 1 H nuclei depends on several factors: - dihedral angle - geminal coupling - number of covalent bonds between these two nuclei - long range coupling

• Stereoselectivity. The preferential formation of one stereoisomer over another in a chemical reaction. If the stereoisomers are enantiomers, one speaks of enantioselectivity [quantified by enantiomer excess]; if they are diastereomers, one speaks of diastereoselectivity. The term enantioselective may be applied to the ultimate outcome of a sequence of reactions, even if individual steps are diastereoselective. • Stereospecific. A reaction is termed stereospecific if, in such a reaction, starting materials differing only in their configuration are converted to stereoisomerically distinct products. According to this definition, a stereospecific process is necessarily stereoselective, but stereoselectivity does not necessarily imply stereospecificity. Examples: Bromine addition to cis- and trans-stilbenes The use of the term “stereospecific” merely to mean “highly stereoselective” is discouraged.