Chapter 8: Addition Reactions

Transcription

1 Chapter 8: Addition Reactions Addition Reactions to Alkenes (Section 8.1) Markovnikov s Rule (Section 8.2) Stereochemistry of Ionic Addition to Alkenes (Section 8.3) 2 S 4 Additions to Alkenes (Section 8.4) 2 Additions to Alkenes (Section 8.5) xymercuration/demurcuration (Section 8.6) ydroboration/xidation (Section 8.7) Addition of 2 and Cl 2 to Alkenes (Section 8.12) Stereochemistry of Dihalide Additions (Section 8.13) alohydrin Formation [Net Addition of X-] (Section 8.14) Divalent Carbon Compounds: Carbenes (Section 8.15) xidations of Alkenes (Sections ) Additions to Alkynes (Sections ) xidative Cleavage of Alkynes (Section 8.20) Applications in Synthesis (Section 8.21) Chapter 8 Relevant Text: Pages

2 Addition Reactions: Addition to Alkenes Addition C C A B A C C B ave Already Looked at Addition of 2 (ydrogenation) Will Now Add Additional Reagents to ur Arsenal X (I,, Cl) 2 2 S 4 2 Cl 2 I 2

3 Why Do Additions to Alkenes Work? Conversion of π Bond to 2 σ Bonds Typically Energy Favored Two σ Bonds igher Energy than ne π + ne σ verall Process is thus Typically Exothermic π Electrons are Exposed (ABVE and BELW sp 2 Plane) π Bonds Good at Capturing Electrophiles ( +, Lewis Acids, X 2 ) tal Ions With Vacant rbitals Also Good Electrophiles Let s Look at the Addition Reaction of a ydrogen alide

4 Addition Reactions: X to Alkenes C C General rder of X Reactivity: I > > Cl > F Usually Dissolved in Solvent (C 3 C 2, C 2 Cl 2 ) Can be Bubbled Through Solution as a Gas Addition of Cl not Generally Useful (Works w/ Silica Gel)

5 Addition Reactions: to Alkenes C C π Bond (Nucleophile) Protonate Carbocation Intermediate Carbocation Captured by (Nucleophile) Added (or other X) Addition in Two verall Steps + and Carbocation are the Respective Electrophiles This is a SYMMETRIC Alkene ASYMMETRIC ALKENES?

6 Markovnikov s Rule: to Alkenes C 2 Cl 2, 0 o C MAJR 2-omopropane is Major Product MINR (TRACE) nly Very Small Amount of 1-omopropane bserved True With ther Alkenes C 2 Cl 2, 0 o C MAJR MINR (TRACE)

7 Markovnikov s Rule: Why? C 2 Cl 2, 0 o C MAJR MINR (TRACE) Product Distribution Explained When Looking at Intermediates Recall Discussion of Carbocation Stability (2 > 1 ) Major Product Formed From More Stable C + Intermediate Less Stable Carbocation More Stable Carbocation

8 Markovnikov s Rule: C + Stability Less Stable Carbocation More Stable Carbocation We Know 2 Carbocations More Stable Than 1 Major Product Formed From More Stable C + Intermediate ans TS in 2 Carbocation Pathway Lower in Energy Lower Energy of Activation Activation Energies in 1 Carbocation Pathways Much Larger

9 Markovnikov s Rule: Summary MARKVNIKV S RULE: In the ionic additions of an unsymmetrical reagent to a double bond, the positive portion of the adding reagent attaches itself to a carbon atom of the double bond so as to yield the MRE STABLE CARBCATIN as an INTERMEDIATE Cl Cl I Cl I I Recall Bond Polarization: δ I δ Cl This Addition Preference is Called REGISELECTIVITY

10 Stereochemistry in Ionic Additions Top Capture C 3 + C 3 C 3 Bottom Capture Just as We Saw in S N 1: C + as TW FACES Top and Bottom Attack Give Two Stereochemical Products R and S Enantiomers Formed as a Racemic Mixture (50:50)

11 2 S 4 Addition to Alkenes S S S 3 C C C C Must Add CLD Sulfuric Acid; Form Alkyl ydrogen Sulfates Regioselective Reaction: beys Markovnikov s Rule Note chanistic Similarities w/ X Addition to Alkenes

12 Alcohols From Alkyl ydrogen Sulfates S 3 2 YDRLYSIS Reaction of Alkyl ydrogen Sulfate Simply eat the Sulfate in Water Net Reaction is Markovnikov Addition of 2 to Alkene Used in ne Industrial Ethanol Making Process

13 Addition of 2 to Alkenes: ydration C C + 3 YDRATIN Reaction of an Alkene Acid Catalyzed Addition of 2 Across Double Bond Net Reaction is Markovnikov Addition of 2 to Alkene We ve Seen a Similar Reaction: Acid Catalyzed Dehydration Carbocation Rearrangements Possible w/ Dehydration Reactions What is the MECANISM for this reaction? Know this!

14 xymercuration-demercuration XYMERCURATIN: C C g(ac) 2 TF gac DEMERCURATIN: Na, NaB 4 gac Net Reaction: Markovnikov Addition of 2 to Alkene Both Reactions Quite Rapid; Alcohol Yields Usually > 90% NaB 4 : Sodium Borohydride Delivering Agent

15 xymercuration-demercuration (2) Pr C C g(ac) 2 TF/ 2 Pr gac Na, NaB 4 Pr g(ac) 2 gac Na, NaB4 TF/ 2 Added Benefit of xymercuration/demercuration: C + REARRANGEMENTS Seldomly bserved Consider Example Seen on Next Slide

16 xymercuration-demercuration (3) 1. g(ac) 2, TF/ 2 2. Na, NaB 4 gac g Stabilization gac Would Expect 2 Carbocation to Rearrange to 3 Added C + Stabilization from g Atom Prevents Rearrangment Useful ydration Process for Avoiding Skeletal Migrations

17 ydroboration xidation Reactions B 3 : TF ydroboration (C 3 C 2 C 2 ) 3 B 2 2, Na xidation ydroboration: Addition of and B to Alkene Neutral Boron has 3 Coordination Sites Get Trialkyl Boranes as an Intermediate (Tripropylborane) xidation: 2 2, Na xidize to Trialkylborate Ester xidation Followed by a ydrolysis, Cleaves Borate Ester ANTI-MARKVNIKV Product (Good for 1 Alcohols!)

18 ydroboration xidation Reactions (2) We ntioned anti-markovnikov Regiochemistry Reaction also Proceeds with SYN Stereochemistry 1. B 3 : TF , Na and Delivered anti-markovnikov to the SAME FACE of the π Bond Sections 8.8 and 8.9 Deal w/ chanistic Aspects. This is Interesting, but is NT Testable Material (You May mit)

19 Addition of Cl 2 and 2 to Alkenes 3 CC CC 3 Cl 2-9 o C 3 CC CC 3 Cl Cl 3 C 2 CC C 2 Cl 2-9 o C 3 C 2 CC C 2 Cl Cl 2-5 o C + Enantiomer btain Vicinal Dihalides as Reaction Products Want to use a Non-Nucleophilic Solvent (Due to Intermediate) Important to Run Reactions in Dark (Avoid Radicals)

20 General chanism of Dihalide Addition C C - - Intermediate is a BRMNIUM IN (in 2 Case) Nucleophilic Solvents Can Capture (pen) omonium Ion omonium Ion pening is S N 2 Anti Addition of 2

21 Stereochemistry of Dihalide Additions Can pen Symmetric omonium Ions at Either Carbon Always (for now) Anti (Trans) Addition of X 2 Reaction Products Are Enantiomers Racemic Mixtures (50:50) in Symmetric omonium Ions Will Get Excess of ne Enantiomer in Asymmetric Cases Stereospecific Reactions: ne Stereoiomeric Form of the Starting Material Reacts in Such a Way to Form a Specific Stereoisomeric Form of the Product

22 alohydrin Formation C C 2 Intermediate is Still a BRMNIUM IN (in 2 Case) Nucleophilic Solvents Can Capture (pen) omonium Ion 2 pens the omonium Ion; Another 2 Deprotonates Product is alohydrin Net X- Addition to Alkene Still Can Get Stereoisomeric Products (pen Either End)

23 Divalent Carbon Compounds: Carbenes C 2 N N Diazomethane eat or Light C 2 + N N thylene (A Carbene) Common Way of Generating Carbenes (Divalent Carbon) Diazomethane: 3 Resonance Structures (Draw thers??) Carbenes are ighly Reactive Species; Short-Lived Excellent Utility is in the Synthesis of Cyclopropanes Let s Look at Some Reactions Making Use of Carbenes

24 Divalent Carbon Compounds: Carbenes C C + C 2 C C C 2 KC(C 3 ) 3 CCl 3 Cl Cl C 2 I 2, Zn(Cu) alogen Substituted Carbenes from aloforms (CCl 3, etc.) Last Reaction is Called the Simmons-Smith Reaction

25 xidation: Syn Dihydroxylation Propene 1. s 4, pyridine 2. Na 2 S 3 / 2 1,2-propanediol (propylene glycol) C=C is xidized by s 4 Addition of ydroxyl Groups Proceeds w/ SYN Stereochemistry Can Also use KMN 4 (More Powerful, May Cleave Diol) If Using KMN 4, Want CLD Reaction Temperatures s 4 is Expensive; Can Use Catalytically if NM is Added

26 xidation: Syn Dihydroxylation (2) s 4, 25 o C Pyridine s smate Ester Syn Addition Due to 5-Centered Transition State Transition State Same for KMN 4 xidations Cleavage of smate Ester Does Not Change C- Stereochem

27 xidative Cleavage of Alkenes KMn 4, Na 2, 2 1. KMn 4, Na C Diol Believed to be Intermediate in Cleavage Reaction Unsubstituted Alkene Carbons xidized to Carbon Dioxide Monosubstituted Alkene Carbons xidized to Carboxylates Disubstituted Alkene Carbons xidized to Ketones

28 ow You May See xidative Cleavage An Unknown Alkene (C 8 16 )GivesTwo Products When Treated w/ ot KMn 4 : C KMn 4, 2 Na, The Products are a Carboxylic Acid and a Ketone, So ur Alkene Must Be Trisubstituted. We Don't Know if it is CIS or TRANS, but we Can Put the Rest of the Structure Together: or

29 zonolysis of Alkenes Et 1. 3, C 2 Cl 2, -78 o C 2. Zn/Ac Et , C 2 Cl 2, -78 o C 2. Zn/Ac Milder Conditions than Treating w/ KMn4 Workup w/ Zn/Ac xidative Cleavage (Ald and Ket) Go Through Exceptionally Unstable Intermediate (zonide)

30 Dihalide Addition To Alkynes 2 CCl 4 2 CCl 4 Cl Cl Cl Cl 2 CCl 4 Cl Cl 2 CCl 4 Cl Cl Addition Reactions, Just as in Alkenes (adds nce or Twice) Anti Additions, First Product Usually a Trans Dihaloalkene Can Get Relatively Good Trans Dihaloalkene Yields (1 eq X 2 )

31 Addition of X to Alkynes geminal dihaloalkane Addition Reactions, Just as in Alkenes (adds nce or Twice) Final Product Typically Geminal Dihaloalkene Both Additions Follow Markovnikov s Rule (explains gem.) Alumina Accelerates Reaction Rate (as seen w/ Alkenes)

32 xidative Cleavage of Alkynes Et 1. 3, C 2 Cl 2, 2. Zn/Ac + Et i Pr Ph 1. 3, C 2 Cl 2, 2. Zn/Ac i Pr + Ph Et 1. KMn 4, Na 2. Ac + Et Can Use Either zonolysis or KMn 4 as with Alkenes Products of the xidative Cleavage are Carboxylic Acids

33 Anti-Markovnikov Addition peroxides peroxides Addition of Peroxides (RR) ANTI-MARKVNIKV Goes Through a Radical chanism (Chapter 10) Right Now Focus on Regiochemistry (Know the Reaction)