Monosubstituted Cyclohexanes Substituents can occupy an axial or

Monosubstituted Cyclohexanes • Substituents can occupy an axial or equatorial position • Equatorial is preferred by larger groups. Why? 7. 3 Monosubstituted Cyclohexanes. Conformational Analysis 1

1, 3 -Diaxial Interactions • 1, 3 -Diaxial Interactions: van der Waals repulsions between an axial substituents on a cycloalkane ring 2

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Problems 1) What is the energy cost of a 1, 3 -diaxial strain in methylcyclohexane? 2) What about bromocyclohexane? 3) Which of the two molecules above will have a higher percentage of its molecules in the equatorial conformation?

More on Ring Flip • Note that the “up” substituent remains up and the “down” substituent remains down after chair interconversion 7

Disubstituted Cyclohexanes 1 -chloro-2 -methylcyclohexane • Trans: the two groups have an up-down relationship • Cis: the two groups have a down-down (or upup) relationship 8

Conformational Analysis • For disubstituted derivatives, the larger group will preferentially occupy the equatorial position 7. 4 Disubstituted Cyclohexanes 9

Problem 1) Which subsituent will most likely occupy the equatorial position for a greater amount of time in cis-1 -chloro-2 -methylcyclohexane? 2) Prove this with calculation.

Polycyclic Molecules • Polycyclic molecules: compounds with two or more rings fused together – Spirocyclic: two rings that have only a single common atom – Bicyclic: two rings that share two or more common atoms 11

7. 6 Bicyclic and Polycyclic Compounds 12

Classification and Nomenclature • Fused and bridged bicyclic compounds 7. 6 Bicyclic and Polycyclic Compounds 13

Naming Bicyclic Systems • Indicate the number of rings using the prefix “bicyclo-” • Indicate the bridge lengths – Number of atoms connecting one bridgehead atom to another (excluding the bridgehead atoms) – Separate by full periods and place in square brackets. • Cited in decreasing order of size (e. g. [3. 2. 1]) • the name of the hydrocarbon indicating the total number of skeletal atoms

Problems • Name the following polycyclic molecules: Norbornane Decalin • If you were just given the IUPAC names for a couple of bicyclic molecules, how would you tell the difference between a fused and a bridged variety?

Cis and Trans Ring Fusion: Decalin 7. 6 Bicyclic and Polycyclic Compounds 16

• Each ring in cis-decalin can undergo ring flip • Ring fusion causes trans-decalin to be conformationally locked 17

Ring Fusion with Small Rings • Bicyclic compounds with small rings are restricted to cis ring fusion • Trans fusion would incur too much ring strain 7. 6 Bicyclic and Polycyclic Compounds 18

Steroids • Organic compounds with 20 carbon, tetracyclic core – Variations in substituents dictate biological activity 7. 6 Bicyclic and Polycyclic Compounds 19

Steroids • Many consist of all trans-fused rings – No conformational change • Many have methyl groups at C-10 and C-13 7. 6 Bicyclic and Polycyclic Compounds 20

Stereochemistry of Cycloalkene Reactions Addition Reactions • Syn-addition: • Anti-addition: 7. 9 Stereochemistry of Chemical Reactions 22

Stereochemistry of Bromine Addition • Addition of bromine to an alkene is a highly stereoselective reaction • Exclusively anti-addition – Gives all trans products 7. 9 Stereochemistry of Chemical Reactions 23

Stereochemistry of Halohydrin Formation • Exclusively anti-addition – Gives all trans products

Stereochemistry of Hydroboration-Oxidation • Hydroboration is a stereospecific syn-addition 7. 9 Stereochemistry of Chemical Reactions 26

Stereochemistry of Hydroboration-Oxidation • The oxidation of organoboranes is a stereospecific substitution reaction 7. 9 Stereochemistry of Chemical Reactions 28

Stereochemistry of Hydroboration-Oxidation • The two steps of hydroboration-oxidation result in net syn-addition of H-OH to the alkene • Note that the trans designation of the name has nothing to do with the way H-OH added 7. 9 Stereochemistry of Chemical Reactions 29

Stereochemistry of Hydrogenation • Catalytic hydrogenation is a stereospecific synaddition 7. 9 Stereochemistry of Chemical Reactions 30

Problem • Draw the products for the following reactions