Chemistry of C-C π-bonds Lectures 1-4: Alkenes, Alkynes and Conjugation Handout 1 Handouts will be available at: http://msmith.chem.ox.ac.uk/teaching.html Dr Martin Smith Office: CRL 1 st floor 30.087 Telephone: (2) 85103 Email: martin.smith@chem.ox.ac.uk “When an unsymmetrical alkene combines with a hydrohalic acid, the halogen adds on to the carbon atom containing the fewer hydrogen atoms, that is the carbon that is more under the influence of other carbons. I cannot here enter into a detailed examination of the various facts that permit us to establish such a law.”* *Markovnikov, V. V. Ann. 1870, 153, 228. The Chemistry of C-C π -Bonds - 2 - Alkene and Alkyne chemistry I  Alkene chemistry Structures and influence of orbitals on reactivity: How do alkenes react and why? Typical reactions of alkenes: Nucleophilic reactions Electrophilic reactions Pericyclic reactions Recap of methods for alkene generation Recap of frontier molecular orbitals for simple reactions  Reactions of alkenes: (i) electrophilic addition: HBr/ionic Br 2 HOBr (anti- attack) epoxidation acyloxymercuration Hydroboration - oxidation (ii) pericyclic additions: Ozonolysis of alkenes and reductive cleavage Diels-Alder OsO 4 (iii) free radical additions allylic bromination (comparison with ionic) (iv) catalytic hydrogenation reduction to alkanes  Alkyne chemistry Structures and influence of orbitals on reactivity: How do alkynes react and why? Electrophilic additions – comparison of reactivity with alkenes: Hydration Alkylation Reduction  Conjugation and delocalization in non-aromatic systems Effects of π-bond on structure and reactivity. Structures of conjugated alkenes and alkynes. MO approach to conjugated systems: the allylic cation, allylic radical and butadiene Allylic bromination Modifications to reactivity as a result of conjugation. Conjugate addition reactions: catalysed by acid or by base Kinetic and thermodynamic (1,2 va 1,4 addition) Reactions controlled by charge Reactions controlled by orbitals The effect of the nucleophile: hard and soft nucleophiles and electrophiles The effect of the electrophile Books “Organic Chemistry”, Clayden, Greeves, Wothers and Warren, OUP, 2000. Comments, questions and queries welcome. The Chemistry of C-C π -Bonds - 3 -  The most important feature of alkenes is the π bond Alkenes possess !-bonds and "-bonds H H H H H H C-C !-bond 350 kJ mol -1 C-C "-bond 260 kJ mol -1 133 pm 108 pm  A π-bond is made up of two 2p orbitals A !-orbital results from a combination of two 2p orbitals of two carbon atoms parallel not parallel !-orbital !"-orbital two p orbitals  A consequence of the overlap of p orbitals is restricted rotation and isomerism Br Cl Cl I I Br The Chemistry of C-C π -Bonds - 4 -  Alkenes may be made by elimination reactions (Prof. Dixon’s course). 1. The E2 elimination: concerted and can be stereospecific H X B H X H X 2. The E1 elimination: stepwise, via carbocationic intermediate X R 1 R 2 R 3 R 2 R 1 H H H cation stabilized by !" and/or #-conjugation 3. The E1 CB elimination: stepwise, via anionic intermediate OHO OHO need an EWG O conjugated product [HO - leaving group] H B -  Alkenes may be made by the Wittig reaction (Prof. Donohoe’s course). H O R P Ph Ph Ph R Ph P Ph Ph O ylidcarbonyl The Chemistry of C-C π -Bonds - 5 -  Typical modes of reaction of alkenes [1]. Nucleophilic E + O E + NR 2 E + Alkenes can be electron-rich and are therefore nucleophilic alkene enolateenamine O E + R enol ether  Typical modes of reaction of alkenes: [2]. Electrophilic E + R Alkenes can be electron-poor and electrophilic alkene when R is electron donating, the alkene is nucleophliic O OEt O OEt Nu Nu In this case R = CO 2 Et  Typical modes of reaction of alkenes: [3]. Pericyclic H H O O O H Diene Dienophile The Chemistry of C-C π -Bonds - 6 -  Interactions between molecules: HOMO and LUMO – a recap HOMO = highest occupied molecular orbital LUMO = lowest unoccupied molecular orbital filled orbital of molecule 1 vacant orbital on molecule 2 When two orbitals are brought together they can interact to form new molecular orbitals. In order for these two orbitals to interact they must: If these requirements are met, then the two electrons will prefer to occupy the new bonding orbital (as it is lower in energy) and the result is a covalent bond.  For alkene modes of reactivity: E + R For electron-poor alkene O OEt O OEt Nu Nu For electron-rich alkene R E (+) The Chemistry of C-C π -Bonds - 7 -  Reactions of electron rich alkenes: electrophilic addition reactions  1. Bromination of alkenes Br Br ! on alkene "# Br-Br Br bromonium cation Br Br - lone pair "# C-Br Br Br dibromide product S N 2 inversion The bromonium ion is an intermediate - this means it can be observed, and in special cases, isolated. Note this is distinct from a transition state (which is a hypothetical state in between bond-breaking and bond-forming). Overall: anti- addition of Br 2 across the double bond  Bromination of alkenes is stereospecific Book Definition: “A reaction is termed stereospecific if starting materials differing only in their configuration are converted into stereoisomeric products” This is useful if we relate it to mechanism and hence a pragmatic working definition is: Br Br Br bromonium cation Br Br Br dibromide product S N 2 inversion Bromination of cyclohexene gives only the anti- diastereoisomer – stereospecific? [but we cannot make the trans-cyclohexene] The Chemistry of C-C π -Bonds - 8 - To check for stereospecificity we need to see if alkene geometry is reproduced in the products – examine both cis- and trans- but-2-ene: S N 2 inversion Me H Br HMe Br Br Br Me H HMe Br Br Br Br S N 2 inversion H Me Br HMe Br Br Br H Me HMe Br Br Br Br C 2 symmetric dibromide cis- alkene trans- alkene meso dibromide redraw redraw  2. Reaction with bromine in water: opening of unsymmetrical bromonium ions Br Br H 2 O H Br HO Br Several species can function as brominating agent: Br X [ X = Br, HO, H 2 O ] ! on alkene "# Br-X Ph Br X Ph Br H 2 O Ph OH Br S N 2 inversion attack at most hindered end (why?) (i) (ii) The Chemistry of C-C π -Bonds - 9 -  Development of charge in the transition state can affect regioselectivity development of charge stabilized by phenyl group (more heavily substituted) Ph Br H 2 O Ph OH Br S N 2 inversion Ph Br HO H [see epoxide opening from Prof Dixon’s Course for a similar situation]  A similar reaction can be performed with mercury(II) acetate ‘acyloxymercuration’ ! on alkene Ph Hg OAc Ph Hg H 2 O Ph OH HgOAc S N 2 inversion AcO OAc NaBH 4 Ph OH H Overall: Addition of water across the double bond (compare with hydroboration)  4. Reaction with HBr: Regioselectivity Ph HBr Ph H Br HBr Br The Chemistry of C-C π -Bonds - 10 - Relate to mechanism of the reaction - initial protonation to give the most stable cation: Ph HBr Ph H Br HBr Br Ph H H H H  Radical Bromination: opposite regiochemistry to ionic process (why?) Br Br Relate to mechanism of the reaction: O Ph O Ph O O Initiation Ph O O Ph O O Initiation facilitated by breaking of weak bond H Br Ph O O + Br Propagation Ph O O H [...]... H Me Me H H redraw Me Me H H This means we get overall cis reduction of the alkene  The Chemistry of C-C π-Bonds - 18 - Alkynes Alkynes have two π-bonds that are orthogonal R1 R1 R2 R2 See Prof Dixon’s course for methods to make alkynes via elimination of haloalkenes  Reduction R1 R1 R2 R1 R2 R2 (1): cis selective reduction of alkynes Key point: The alkyne is more susceptible to hydrogenation than...The Chemistry of C-C π-Bonds - 11 - We break weak bonds and make strong bonds in the propagation step Br H Br H Br Br Br Regiochemistry is dictated by addition of the bromine radical to generate the most stable radical  5 Reaction With Peracids: Stereospecific Epoxidation HOMO O O H R O O LUMO H + RCO2H R O O O The Chemistry of C-C π-Bonds - 12 -  6 Hydroboration: stereospecific syn-addition of the... substitution (ring closure) Cl  The Chemistry of C-C π-Bonds - 21 - Hydration of alkynes with Mercury (II) acetate (compare with alkenes) AcO OAc Hg ! on alkyne OAc H2O R H H+ Hg H+ H R HgOAc HO R H2O H+ XR H R H+ H H O R O HgOAc O A useful reaction that leads to the production of ketones from terminal alkynes  Isomerization of alkynes pKa 16 KOH/ROH H heat pKa 25 (i) Disubstitutued alkynes are thermodynamically... simultaneously and hence the cis alkene is produced The Chemistry of C-C π-Bonds - 19 -  Trans- selective reduction H R1 Na H H NH3 (l) H R2 R2 R1 NH3 (l) R2 N H R2 R1 H R2 R1 R1 H Sodium is the reducing agent in this reaction, and ammonia is capable of functioning as a proton source  H Alkylation (and isomerization) H H H H H H H H H H H H H H H H H H H H The significantly increased acidity of alkynes. .. acyoxymercuration/reduction) The Chemistry of C-C π-Bonds - 14 -  Pericyclic reactions involving alkenes  6 Pericyclic reactions: Reaction with Ozone and subsequent reduction (a useful method for the cleavage of C=C bonds) LUMO O O O O O O O O R HOMO O O R O O R R PPh3 O (or SMe2) R O O redraw O O O R Overall: O O R O Ph P Ph R Ph A useful way to ‘unmask’ a carbonyl group R O  The Chemistry of C-C π-Bonds - 15 -... monosubstituted (ii) Terminal alkynes are the most acidic protons Mechanism: use a reversible base to get the thermodynamic product H H H OR H H OR OR OR  The Chemistry of C-C π-Bonds - 22 - Conjugation and has effects on reactivity and reaction outcome OH Br OH Br Kinetic product distribution Thermodynamic product distribution The same ratio of products is obtained regardless of which allylic alcohol... two carbons at the end of the system How can we consider this in terms of molecular orbitals?  The Chemistry of C-C π-Bonds - 23 - Molecular orbital picture of the allyl cation We can consider this as an extension of the simple picture covered on p3: 2 electrons in a ! bond combine 'in phase' vacant p-orbital !-orbital The easiest way to do this is to look at a combination of THREE p-orbitals, which... SAME energy NONBONDING The Chemistry of C-C π-Bonds - 26 -  We can use an extended version to look at two alkenes in conjugation – butadiene Consider butadiene as a combination of two ethene MOs: ANTIBONDING good overlap poor overlap bonding interaction ANTIBONDING increasing energy antibonding interaction Combine two MOs of ethene What does all this tell us about the chemistry of a conjugated alkene... requires the presence of an electron-withdrawing group on the alkene (that leads to a lowering in energy of all the orbitals – covered in more detail in next lecture) O  O Spectroscopic evidence for conjugation Spectroscopic evidence from Infrared (cm-1): O O The Chemistry of C-C π-Bonds - 29 - Spectroscopic evidence for conjugation II Spectroscopic evidence from 13C NMR (ppm) O  Examples of Conjugate Addition... catalysed: O O HCl Cl O H O Cl H O H The Chemistry of C-C π-Bonds - 30 -  Base catalysed process: O O H O H OH O O O H H  O Overall: O O O The better the ability to stabilize a negative charge the better the conjugate acceptor i.e the faster the reaction This can be related to pKa: O EWG H O2N O O NC R RO R2N  The Chemistry of C-C π-Bonds - 31 - Why does conjugation with an electron withdrawing . Chemistry of C-C π-bonds Lectures 1-4: Alkenes, Alkynes and Conjugation Handout 1 Handouts. 1870, 153, 228. The Chemistry of C-C π -Bonds - 2 - Alkene and Alkyne chemistry I  Alkene chemistry Structures and influence of orbitals on reactivity: