Organic Chemistry Notes: Carbonation Rearrangements, Alkene Stability & Reactions, Elimination Chemistry, Epoxides, Alkynes

Carbonation Rearrangements

• Approach starting material carefully; labeling is key.

• Label products, focusing on groups/atoms one or more bonds away from a specific atom (H, Me, etc.).

• Choose the least amount of change during the reaction.

• Catalog all changes.

Unit 3 Lecture 21: Alkene Stability, Naming, & Elimination Chemistry

Alkene Stability

• Alkene + $H_2$ -> Alkane

• Alkene position affects stability.

• Sterics affect stability.

• More non-H substituents lead to greater stability.

• Why is $A \rightarrow X$ exothermic?

  • Illustrated with energy levels: A at -50, B at -27.5, C at -28.5

  • B and C are diastereomers because there is no D.H. The rotation around it bonds

• Source of Alkene Stability: Hyperconjugation

  • Filled $σ$ orbital overlaps with underfilled orbital.

  • $↑$ substitution = $↑$ stability of Alkene.

  • Replace C-H with other #CC

Naming

Descriptive

• "Substituted" vs. Unsubstituted = replace H on:

  • Monosubstituted

  • Disubstituted

  • Trisubstituted

  • Tetrasubstituted

Formalized Naming

• Longest carbon chain that includes the alkene (anezene).

• Number the alkene so that the 1st # is smallest.

• I root: 2 alkenes = diene

  • Example: (3R)-3-bromo-1,5-hexadiene

  • Example: 1-pentene -> pent-1-ene

  • Example: (4R)-4-bromo-1,5-hexadiene

Alkene Stereochemistry

• Trans alkene vs. cis alkene

  • trans-2-butene vs. cis-2-butene

• cis & trans only used in naming if disubstituted alkene

• MedCI cis to each other; Med Et are trans

• Name: root: 2-pentene sub: 3-chloro

  • 3-Chloro-2-pentene

E & Z for Alkenes

1. For substituents on each carbon of alkene, assign priority 1 and 2.

2. If 1s are cis: Z; 1s are trans: E

   • Cyclic Alkenes

     • Carbon chain must be cis to each other for ring sizes 7 and smaller.

     • cis cyclooctene vs trans cyclooctene

Elimination Chemistry to Form Alkenes

• Remove $\beta$H & LG to create $\pi$ bond between $\alpha$ & $\beta$ atoms

Stepwise Mechanism: E1

• LG leaves, then Acid/Base

• Same cation limitations as SN1

• $II + +20 \downarrow activate LG$

• LG \rightarrow leaves P - H & AlB 7 0 -H OH_2

• \rightarrow & H20 OH2 YL \rightarrow \ -H conj base

• $B \alpha \beta LG cong base (sulfuric acid) - i OH + H-OSO_3H$

• E1 \rightarrow Alkenes H30 D E GusO3H \downarrow activate LG # E -- Bi - H_20

• So LG leaves -osB_3 make cation 3D & focus on \beta , A's

• Rotate so it has appropriate orientation to make it bond (1H on line either up or down Et B2 20Hz H36 & C CH3 ⑦ * IP…. Cha , CH3

• Bi v Et es C es - Me B3 me** B . H pointing down Et #EtT me Et

• : ① …2 GHz M H2) Acid/Base H - Orbs C * filled Et orb - = Alkene Formation Orbs H20 nb0sp3 H20 filled Orb ⑭ ⑭ I ⑭t O CH empty orb empty orb * CH nbcp

Lec 22: Elimination E2 Chem

• Requirement: Strong base ($RO^-$ or stronger, like $NR_2$)

• Concerted: Grab $\beta$H, form $\pi$bond, kick out LG in one step.

• RateE2 = K [base] [elec-1G] &Energy Diagram

• Why is EC exothermic? -> Bonds It OCH o OH Break Form ET X in E due to charge Stabilization OCL TCC SM E2 & pdts & should be ENDOTHERMIC blc it weaker than 0 Charges dictate reactivity O > LGO Stronger base -> weaker base EXOTHERMIC

• E2 requires a specific conformation

  • $\beta$H and LG are anti coplanar

E2 vs SN2

• Electrophile Structure

  • $↑$ $\beta$ branching - decrease in SN2 rate

  • No effect on E2

• How should product energies compare?

  • Compare bonds & Charges

  • $↑I$ branching expect large$↓$ in SNz rate E2 and SN2 are determined by kinetics (will make the easiest thing first)

• Base Size Effect on SN2 vs Ez

  • $↑$ SN2 nuc size, d SW2 rate expect $↓$ SNzw/ sterics of base/nuc stronger base = E2 $↑$ base strength, T$↑$ E2 blc it require AlB w/ No bases, if E2 is an option, we will only see E2

  • Lithium Diisopropul Amide: LDA

Lec 23: Effects of Base Size & Strength on E2 (predict SM)

Regiochemistry

• Which reactive site does chem?

• How does base size affect E2 regiochemistry

Approach

1. Label $\alpha$ & $\beta$ Spots

2. Get $\beta$ As anticoplanar

   • ex. NH2 E E2 small TS base w/ does small NOT have base additional (GNH2) sterics in /Meoo TS also small)

• Cl -Energy Diagram

  • E2 with small base (ONH2) - 4 exothermic - down hill 1 Ez exothermic -- - - - Dotted Line is our kinetic assumptio

1. Thermoanalysis * of alkene pats ---- SMALL BASES follow that

2. Apply kinetic Assumption - & assumption & - & Ckinetics match thermo 11 mono subbed alkene

3. DoesTs Analysis affect assumption ? i' OB,B2 * -sterics I Bi ob = hyperconjugation/ Orbital overlap -beneficial H-bonding 9 trisubbed alkene

4. Kinetic Product is major product SM S pd + S - in this case Bi

Large Base Analysis (LDA)

• Big Base Major pot is " B2 B , S Predicting SMS of EC Chem

Approach

1. Regiochem

2. Stereochem

Lec 24: Alkenes Stepwise Reaction

AlB Halonium Alkene Rxns

• Carbocation Intermediates Stepwise "addition" mechanism

• Make best cation possible

Ai) Alkenes as bases

• + H -C -- & ↑ E I (C) as base ((2) as a base - H -2 + 10 it - - & -20 H -Cl (cationIntermediate BAD! locations are a NO !!

• Aii)M + D A as base B as Base D-Er - & We boron Sh - 8 total pdts too P Mill * a # Aiii) Alkene Isomer: cation Constitutional isomer (e.g. 1-butene -> 2-butene) Stereoisomer (cis vs trans) (E orz) 2 & - ↳ ↳H - V OSO3H ~ - H ⑦ ⑦ Y - #H OSO3H H H -DB & 2 Hy H -D * H Mead" H Me Me BI Air) Alkene Polymerization Alkenes as bases, Alkene as nuc, elimination cat ↓ I H-OSO3 H & x Mech Dimer (two of same IIH-5503H ↑ molecules react - together) ↓ Al 00 SO3H H S3H alkene as ↳ # -- -> Ya vinyl chloride Xc PVC (polyvinyl Chlorich

"Ohium" is a 3 membered ring w/ a G Charge

Halonium Chemistry

• Chlorine or Bromine in 3-membered ring

Bi) Antiaddition of X2 to alkene

• (Xs add to opposite faces of alkene)

• 1st: From halonium 2nd : Attack halonium

• Halonium Formation Br2 Top Bra

• Thought Experiment: O bond resonance - Br - use resonance analysis to put 50 on atoms CG 5 & S ① Bu 00 o L Br

• 7 D3C A *" 000( ~ CH3 / AtomsStay stationary, - more bestpIC filled octets * ① so so followinek E ↳* ⑦ Br mid biC 30 cation worst DIC

Nuc Attacks Halonium Orbs

• Nuc attacks carbon *CBr wI highest reaction w/ bottom bromonium ⑦ Bu nus ↳ DS - Br * D n-> & H py o use Br LG nus Bu Br & H H33 byAs / ↑" Br Br LG nuc Bro Attacked bottom Bro Attacked top bromonium bromonium

Bii)

• 1 halonium make halonium w/ solvent #ge 2. solvent attacks at - 3. and I base - nuc comes front ↓ ↓ back in opposit G - 1. 19 ↑ - L *so t Fur a * OHz

Lec 26: Concerted Alkene Rxns

Syn Additions to Alkenes

• (concerted rxns

② Hydrogenation

• (syn adding of H & H to alkeneCs ( major pot easier to do = less sterics * our catalyst for this is: Palladium on Carbon Pd/C

• ex - + H -H - H D2 w/ Allenes (Stereochem) Add Wedge/dash to DS

• Mechanism Pd/C

⑪ Epoxidation

• epoxide & Coxirane O mCPBA * Reagent: par-acid Rot- #NorProper benzoic Acid L - R bote%! / * know this mechanism * H -> · H /

② Dihydoxylation

*Reagent : HO-OH osmium retroxide -> cat Os 0x N + HO-OH osmium retroxide ↑& me predict pot based on descriptio
*similar to hydrogenation arrows

⑦ Hyboration

• syn addition of H &B to nea PS #BR2 Hz) H (HBR2) 12 Regiochemistry

• permanent dipole in HBR2 induces a matching D31S05810 3.. # dipole in alkene your go on best C - - H ②Sterics Hg H… .. B B # 9-BBN This reagent makes ERICS the determining factor in regiochem

• - - - 1 ,5-cyclooctadiene BH ↳ a H Laxx H # ⑮ [ + 9BBN (n -p=8) B=

Fa Oxidation of Hydroboration pdt

• Replace C-B bonds w/ C-OH bonds, * Reagent: H202 , HOO H2O keepStereochem) + Me -OH - Me D3D >H 0H E t Hz H B meD Ho B(OH)4 H202 , 120 % meme C-OH bords keep Stereochem)

Lec 26: epoxides

Epoxides 8 1. Synthesis

• IA. MCPBA and alkene Alkene + per Acid -> epoxide + Acid side pdt

• IB. SN2 Chem - epoxide +10 H -0 O Pra = 15 + NaH- > L Hy + Na OTf OTf sodium good thermo , bad Herme AlB hydriche LGO is better than NucO ring Strain

Epoxides as electrophiles

• (ring strain is the main "leaving grp

• 2A). Strong NUC * SN2 reactivity & preferences * Good Nuc: OCN, N38, ROO, RSO, R3N

• new #10CR3 Specific for epoxide elec nvc attacks - least 2Ai of sterically encumbered n # + OCN - epoxide Carbon i ⑧o &-du ↳ ROG alkoxide pdt

• How are A and O ⑦ How are C and 90 B related?

• - Fan " ·Conf pageon · o conf o const * o const ",& O enant ⑦ 2. o diast night · enant o diast only draw right one as a product!

2Aiv) arpanion Nucleophiles

• (OCRs) ⑦ ALL STRONG BASES MeO = OCH3 iPro= - IIT = PLE * know this Phenylanion = Phenylanion Benzene ring missing H, add a LithiumCounterion (LiORO) Magnesium X Counterion (xMgOR) "Organo lithium reagents" "Grighard Reagents" ⑧ ⑦ ⑦ Synthesis: R-X + &Li + RLi + LiX I Synthesis: RX + Mg e Ro MgOX (keep charges balanced

2v) Carbanions as nucs w/ epoxide eles constitutional G P + PhMgC -# +Mgc PhOMgOCI Top bott alcohol pat (ROH) # Alkoxide pdts (roo) I mild Hs [neutralize 00 to OH] 2B) weak nucs attack epoxides [require Acid catalyst] Acidic Conditions: "Anion" Intermediate (Lec 24, haloniums ( Nuc attacks site w/ best 80, sterics CONT matter

• 2 Bii) Comparisons 2Bi HO OcI we Cas & ⑦ & % MH? 1 . mCPBA i Cat H -OH2 - ↓ by""A T -> ↳ nu 10 a OCI H ⑪ - 2. Onium H - intermediates C) ↳ ↓"oxonivi P … react& carbon CH3 w/ highest @ (from cat) H20 -> DzS "↑ D me stichiometric) to H ⑪Mon 2212 , Ha i OH 2 &H2 · by""A L G Do met 220 S HO O OH2

Lec 27: Alkynes

• Alkynes (R- CEC -R) carbanion & pla = 35 Pka = 25 & & * R -CEC -H + NH2 X R -c = co + NHz

• ((sp) -H K = 10 s N(sp3) -H charge: neutral no difference electronegativity: ENCC) < ENCN) predict H-W to be more acidic resonance: no data show our prediction is wrong inductive effect: none D only other difference is hybridization c (sp1 vs N(sp3) better stabilizes@

Hydrogenation cat excesstz

• Pace alkane - R H R-CEC -R I excessH2 & H & c=C alkene ca+ pd/BaS4 * / (syn addition of He to Barium Sulfate R "Poisoned Catalyst" alkyne ( 1) D2 Pd/C (syn D2 addition) & H PH M 1 R RI R RI BaSO4 = Lindlar's Catalyst Y & -r H P

Lecture 28: Squalene Cyclization

• 2 , k 3-oxido squalene k k * - * & Tno -> S of H ↳ ↓ eartaciscie enzyme 11HA * - - k & an elimination ! ↳ rearrangements G H o N Ha [ Label relevants& methyls on pdt & SM

• O ① O "Not side mcPBA pot of MCPBA on · triflate tosylate mesylate

• R-Mgx

• H-0503H

Syn-Addition Alkene Reactivity

Reaction : Hydrogenation
, Syn-addition of H/D & H/D to (former) pi carbons
Reaction : Epoxidation
,Replace double bond with epoxide at (former) pi carbons