Revision Lecture 2.pdf

CH3E9 2017 - Compulsory = 5 marks Draw the structures Stereochem and use FMO HOMO defines the ‘character’ of electrocyclisation ring closing and opening Ψ2 = HOMO in thermal reaction Ψ4 Ψ3 Ψ2 Ψ1 ANTARAFACIAL = CONROTATORY in TS CH3E9 2016 - Optional = 8 marks = 2 marks (ii) Using FMO predict structu...

CH3E9 2017 - Compulsory = 5 marks Draw the structures Stereochem and use FMO HOMO defines the ‘character’ of electrocyclisation ring closing and opening Ψ2 = HOMO in thermal reaction Ψ4 Ψ3 Ψ2 Ψ1 ANTARAFACIAL = CONROTATORY in TS CH3E9 2016 - Optional = 8 marks = 2 marks (ii) Using FMO predict structure… …and clearly show stereochem HOMO defines the ‘character’ of electrocyclisation ring closing and opening Ψ2 = HOMO in thermal reaction Ψ4 Ψ3 Ψ2 Ψ1 ANTARAFACIAL = CONROTATORY in TS (i) Using FMO predict structure… …and clearly show stereochem Diene is relatively electron rich (HOMO) and dienophile is relatively electron poor (LUMO) Map HOMO (thermal = Ψ2) onto diene and LUMO onto the dienophile Ψ2 HOMO Secondary orbital interaction promotes endo TS ENDO product SUPRAFACIAL LUMO (ii) ZnCl2 what and why…? ZnCl2 = lewis acid Interacts with C=O and lowers LUMO energy level Increases the rate of reaction CH3E9 2017 - Optional = 10 marks (i) Using FMO explain… Ground state (ii) Propose a mechanism…use FMO to explain why its thermally allow (ii) Recall CH3E9 2015 - Optional = 5 marks ʋ = 1680 cm-1 Predict structure… Pseudo equatorial …and explain stereochem E Number your skeleton for suspected sigmatropic rearrangements NOTE – involves σ-bond migration, usually C-H, C-C or C-Het (C-O in this case) 1 Z 2 3 1 If you have a choice put big groups eq In some cases you have no choice e.g. double bonds set ax and eq orientations of Me groups 3 2 Pseudo axial 1 eq = dash 1 2 1 2 3 1 2 3 1 2 1 3 3 E E ax = dash 2 3 3 2 CH3E9 2014 - Optional Propose a mechanism Initiation – generate chain carrier Vinyl radical unstable; 1,5-translocation possible 1 2 3 5 4 5-exo-trig cyclisation then possible Mechanistic proof – use Bu3SnD Reduction when XS Bu3SnH used CH3E9 2023 - Optional Upon treatment with acid, 31 isomerises into a mixture of 32, 33 and 34. Draw mechanisms for the formation of 32, 33 and 34 and predict the major isomer formed. [30%] Answer: adapted from Macromolecules 2011, 44, 1831–1840. Can be reached by applying knowledge gained from the notes and worked examples. 1 mark for formation of the first carbocation 1.5 marks for first hydride shift (1 mark) followed by elimination (0.5 mark) 1.5 marks for methyl shift (1 mark) followed by elimination (0.5 mark) 1.5 marks for second hydride shift (1 mark) followed by elimination (0.5 mark) 0.5 mark for identifying either tetra substituted alkene isomer as most stable (33 slightly more stable according to calculations but the difference is small so I will accept either 33 or 34). CH3E9 2016 - Compulsory = 5 marks Draw the structures Explain outcome and stereochemistry showing key intermediates Initiation – generate chain carrier Reduction when XS Bu3SnH used 5-exo-trig cyclisation with Ph equatorial give the major product CH3E9 2016 - Compulsory 3D representations Triplet considered to be ground state Comment on how R affects orbital occupancy and multiplicity Electron rich R-groups with lone pairs can stabilise sp2-singlet carbene through donation into the empty p-orbital, promoting electron pairing. This is best represented by drawing resonance forms Comment on how R affects stereochemical outcome of the reaction with an alkene CH3E9 2017 - Compulsory Draw 3D representations of the ground state structures of carbenes 1 and 2. Carbene 2 reacts with cis-but-2-ene (3) stereospecifically to give cyclopropane 4. Draw a mechanism for this reaction and then use molecular orbitals to explain why a direct linear approach for the reaction of 2 with 3 is disfavoured. CH3E9 2017 - Compulsory 3D representations …use molecular orbitals to explain why a direct linear approach for the reaction of 2 with 3 is disfavoured Linear approach disfavoured on the grounds of orbital symmetry. During linear approach, out of phase orbital interactions are unavoidable mechanism A sideways on approach is preferred as this maximises the ‘in-phase’ orbital interactions CH3E9 2016 – Optional Identify 10 and 11.. 10 11 Draw mechanisms 10 → 12 Explain regiochem 10 12 Draw mechanisms 11 → 13 Explain regiochem 11 13 CH3E9 2013 - Optional Rationalise the outcome = draw a mechanism Diazo carbonyl and ring contraction suggests Wolff rearrangement Formation of a ketene is therefore essential Drawing a concerted or stepwise process is acceptable from a mechanistic point of view However consider that you are asked to identify the first reactive intermediate formed… Carbene (structure discussed above) CH3E9 2016 – Optional Intermediate 16 3 is an isocyanate formed by rearrangement of carbonyl azide intermediates formed via two slightly different pathways Mechanism from 15 Curtius rearrangement Carbonyl azide intermediate is formed from azide substitution of the acid chloride Concerted migration and loss of N2 results in formation of the isocyanate (KEY) N next to the carbonyl is an electron deficient ‘nitrene’ though the nitrene is not isolable Mechanism from 14 Schmidt rearrangement Carbonyl azide intermediate is formed in the presence of hydrazoic acid via addition of the azide to an acylium ion Concerted migration and loss of N2 results in formation of the isocyanate (KEY) N next to the carbonyl is an electron deficient ‘nitrene’ though the nitrene is not isolable Structure & mechanism 17 formation of urea via addition of the amine to the isocyanate Structure & mechanism 18 (only structure required in Q) 3 → 4 formation of an amine. Addition of water to the isocyanate results in formation of carbamic acid which readily decarboxylates to give the amine and CO2 CH3E9 2012 - Optional Mechanism & structures Favourski rearrangement so inclusion of the cyclopropanone intermediate is essential Usually have reagents that act as a base and then nucleophile e.g. NaOMe in MeOH Methoxide acts as base first to mediate cyclopropanone formation Methoxide then acts as a nucleophile to attack the strained ketone leading to collapse of the intermediate Labelling experiment shows that with a symmetrical intermediate the ‘collapse’ can occur through either α-carbon CH3E9 2017 - Optional (-)-Menthol (1) is sequentially oxidised to give lactone 3. Suggest reagents for the oxidation of (-)-Menthol (1) to (-)-Menthone (2). Provide a mechanism for the formation of 3 from 2 and comment on the regiochemical and stereochemical outcome of the reaction. (25%) Suggested reagents for the oxidation of menthol to menthone = chromic acid / dichromate Mechanism Regiochemistry – most electon rich group migrates i.e. C1-C2 migrates preferentially Stereochemistry – sp3 orbital of migrating group has good overlap with the O-O σ* so migration occurs with minimal reorganisation.