Formation of glycols with Syn Addition Osmium tetroxide Syn addition also KMnO 4

Anti glycols Using a peracid, RCO 3 H, to form an epoxide which is opened by aq. acid. Peracid: for example, perbenzoic acid The protonated epoxide is analagous to the cyclic bromonium ion. epoxide

An example Are these unique? Diastereomers, separable (in theory) by distillation, each optically active

Ozonolysis Reaction can be used to break larger molecule down into smaller parts for easy identification.

Ozonolysis Example For example, suppose an unknown compound had the formula C 8 H 12 and upon ozonolysis yielded only 3-oxobutanal. What is the structure of the unknown? The hydrogen deficiency is = 6. 6/2 = 3 pi bonds or rings. The original compound has 8 carbons and the ozonolysis product has only 4 Conclude: Unknown  two 3-oxobutanal. Unknown C 8 H 12 ozonolysys Simply remove the new oxygens and join to make double bonds. But there is a second possibility.

Another Example Hydrogen Deficiency = 8. Four pi bonds/rings. Unknown has no oxygens. Ozonolysis product has four. Each double bond produces two carbonyl groups. Expect unknown to have 2 pi bonds and two rings. To construct unknown cross out the oxygens and then connect. But there are many ways the connections can be made. a b c d Look for a structure that obeys the isoprene rule.

Mechanism Consider the resonance structures of ozone. These two, charged at each end, are the useful ones to think about. Electrophile capability. Nucleophile capability.

Mechanism - 2

Mechanism - 3

Mechanism - 4

Hydrogenation No regioselectivity Syn addition

Heats of Hydrogenation Consider the cis vs trans heats of hydrogenation in more detail…

Heats of Hydrogenation - 2 The trans alkene has a lower heat of hydrogenation. Conclusion: Trans alkenes with lower heats of hydrogenation are more stable than cis. We saw same kind of reasoning when we talked about heats of combustion of isomeric alkanes to give CO 2 and H 2 O

Heats of Hydrogenation Increasing substitution Reduced heat of Hydrogenation By same reasoning higher degree of substitution provide lower heat of hydrogenation and are, therefore, more stable.

Acid Catalyzed Polymerization Principle: Reactive pi electrons (Lewis base) can react with Lewis acid. Recall Which now reacts with a Lewis base, such as halide ion to complete addition of HX yielding 2-halopropane Variation: there are other Lewis bases available. THE ALKENE. The new carbocation now reacts with a Lewis base such as halide ion to yield halide ion to yield 2-halo-4-methyl pentane (dimerization) but could react with another propene to yield higher polymers.

Examples of Synthetic Planning Give a synthesis of 2-hexanol from any alkene. Planning: Alkene is a hydrocarbon, thus we have to introduce the OH group How is OH group introduced (into an alkene): hydration What are hydration reactions and what are their characteristics: Mercuration/Reduction: Markovnikov Hydroboration/Oxidation: Anti-Markovnikov and syn addition

What alkene to use? Must involve C2 in double bond. Which reaction to use with which alkene? Markovnikov rule can be applied here. CH vs CH 2. Want Markovnikov! Use Mercuration/Reduction!!! Markovnkov Rule cannot be used here. Both are CH. Do not have control over regioselectivity. Do not use this alkene. For yourself : how would you make 1 hexanol, and 3-hexanol?

Another synthetic example… How would you prepare meso 2,3 dibromobutane from an alkene? Analysis: Alkene must be 2-butene. But wait that could be either cis or trans! We want meso. Have to worry about stereochemistry Know bromine addition to an alkene is anti addition (cyclic bromonium ion)

This worked! How about starting with the cis? This did not work, gave us the wrong stereochemistry!

Addition Reaction General Rule… Characterize Reactant as cis or trans, C or T Characterize Reaction as syn or anti, S or A Characterize Product as meso or racemic mixture, M or R RelationshipCharacteristics can be changed in pairs and C A R will remain true. Want meso instead?? Have to use trans. Two changed!!

Alkynes

Structure sp hybridization

Acidity of Terminal Alkynes Other strong bases that will ionize the terminal alkyne: Not KOH Stronger base Weaker base

Important Synthetic Method: Dehydrohalogenation 1. Dehydrohalogenation… An alkyl halide can eliminate a hydrogen halide molecule, HX, to produce a pi bond. RCH=CHR + HX RCHXCH 2 R Strong base Also, if we start with a vinyl halide and a very strong base (vinyl halides are not very reactive). RCH=CHBr RCCH NaH Or rewriting RCHBrCH 2 R RCH=CHR base Recall that HX can be added to a double bond to make an alkyl halide. HX can also be removed by strong base, called dehydrohalogenation. Preparation of alkene

Synthetic planning (Retrosynthesis) Target molecule. Trace the reactions sequence from the desired product back to ultimate reactants. C But typical of synthetic problems side reaction occurs to some extent and must be taken into account. Overall Sequence converts alkene  alkyne Work Backwards….. Starting reactant

More Sythesis: Nucleophilic Substitution Use the acidity of a terminal alkyne to create a nucleophile which then initiates a substitution reaction. Note that we still have an acidic hydrogen and, thus, can react with another alkyl group in this way to make RCCR’ Alkyl halides can be obtained from alcohols

Reactions: alkyne with halogen No regioselectivity with Br 2. Stereoselective for trans addition. RCCR + Br 2  RBrC=CBrR

Reactions: Addition of HX The expected reaction sequence occurs, formation of the more stable carbocation. Markovnikov orientation for both additions. Now for the mechanism….

Mechanism The expected reaction sequence occurs, formation of the more stable carbocation.

Addition of the second mole, another example of resonance.

Reactions: Acid catalyzed Hydration (Markovnikov). Markovnikov addition, followed by tautomerism to yield, usually, a carbonyl compound.

Reactions: Anti Markovnikov Hydration of Alkynes, Regioselectivity Similar to formation of an anti-Markovnikov alcohol from an alkene Step 1, Internal Alkyne: addition to the alkyne with little or no regioselectivity issue. Alternatively Asymmetric, terminal, alkyne if you want to have strong regioselectivity then use a borane with stronger selectivity for more open site of attack. sia 2 BH Less exposed site. More exposed site. Step 1 Step 2 Aldehyde not ketone.

Tautomerism, enol  carbonyl Overall… Step 2, Reaction of the alkenyl borane with H 2 O 2, NaOH would yield an enol. Enols are unstable and rearrange (tautomerize) to yield either an aldehyde or ketone. internal alkyne   ketone (possibly a mixture, next slide) Terminal alkyne   aldehyde

Examples As before, for a terminal alkyne. Used to insure regioselectivity. Get mixture of alkenyl boranes due to low regioselectivity. But for a non-terminal alkyne frequently will get two different ketones

Reduction, Alkyne  Alkene You can use a reduced activity catalyst (Lindlar), Pd and Pb, which stops at the alkene. You obtain a cis alkene. 1. Catalytic Hydrogenation Syn addition If you use catalysts which are also effective for alkene hydrogenation you will get alkane.

Reduction Treatment of alkenyl borane with a carboxylic acid to yield cis alkene. 3. Reduction by sodium or lithium in liquid ammonia to yield the trans alkene. Instead of H 2 O 2 / NaOH Alkenyl borane

Plan a Synthetic Sequence Retrosynthesis Synthesize butan-1-ol from ethyne. Work backward from the target molecule. Target molecule Is read as “comes from”. A big alkyne can be formed via nucleophilic substitution. This is the chance to make the C-C bond we need. Do a “disconnect” here. Catalytic Lindlar reduction Catalytic reduction Lindlar Addition of HBr. Convert ethyne to anion and react with EtBr. 1.BH 3 2.H 2 O 2, NaOH Now, fill in the “forward reaction” details Major problem: make big from small. Be alert for when the “disconnect” can be done. Ask yourself! Do we know how to join any two molecules together to yield an alcohol? Not yet! So how can we get it?How about joining molecules to get an alkene? Not yet!! So how can we get an alkene? Can we get an alkyne from smaller molecules? YES!