1. Addition Reactions of Alkenes

Transcription

1 hapter 8 Alkenes and Alkynes II: Addition eactions reated by Professor William Tam & Dr. illis hang h. 8-1 About The Authors These PowerPoint Lecture Slides were created and prepared by Professor William Tam and his wife, Dr. illis hang. Professor William Tam received his.sc. at the University of ong Kong in 1990 and his.d. at the University of Toronto (anada) in e was an NS postdoctoral fellow at the Imperial ollege (UK) and at arvard University (USA). e joined the Department of hemistry at the University of Guelph (ntario, anada) in 1998 and is currently a Full Professor and Associate hair in the department. Professor Tam has received several awards in research and teaching, and according to ssential Science Indicators, he is currently ranked as the Top 1% most cited hemists worldwide. e has published four books and over 80 scientific papers in top international journals such as J. Am. hem. Soc., Angew. hem., rg. Lett., and J. rg. hem. Dr. illis hang received her.sc. at New York University (USA) in 1994, her M.Sc. and.d. in 1997 and 2001 at the University of Guelph (anada). She lives in Guelph with her husband, William, and their son, Matthew. h Addition eactions of Alkenes 1A. ow To Understand Additions to Alkenes This is an addition reaction: added across the double bond π-bond σ-bond 2 σ-bonds h. 8-3 onds broken onds formed h. 8-4 Since p bonds are formed from the overlapping of π orbitals, π electron clouds are above and below the plane of the double bond lectrophilic electron seeking = and π bonds are particularly susceptible to electrophilic reagents (electrophiles) π electron clouds ommon electrophile, ( = l,, I), g 2, etc. h. 8-5 h. 8-6

2 In an electrophilic addition, the π electrons seek an electrophile, breaking the π bond, forming a σ bond and leaving a positive charge on the vacant π orbital on the adjacent carbon. Addition of to form a σ bond provides an addition product h. 8-7 h lectrophilic Addition of ydrogen alides to Alkenes: Mechanism and Markovnikov s ule Mechanism Mechanism Sometimes do not go through a free carbocation, may go via A h. 8-9 h Markovnikov s ule For symmetrical substrates, no problem for regiochemistry Markovnikov s ule ut for unsymmetrical substrates, two regioisomers are possible same as 3 3 or 3 same as h different from 3 h. 8-12

3 Markovnikov s ule In the electrophilic addition of an unsymmetrical electrophile across a double bond of an alkene, the more highly substituted and more stabilized carbocation is formed as the intermediate in preference to the less highly substituted and less stable one Markovnikov s ule Thus NT h Note: carbocation stability 3 o > 2 o > 1 o h Addition of ydrogen alides Addition of l, and I across a = bond is the electrophile δ δ slow r.d.s fast N h h A. Theoretical xplanation of Markovnikov s ule 3 3 step 1 (slow r.d.s.) 2 o carbocation (more stable) or 3 1 o carbocation (more stable) ne way to state Markovnikov s rule is to say that in the addition of to an alkene, the hydrogen atom adds to the carbon atom of the double bond that already has the greater number of hydrogen atoms h (1 o cation) fast (minor) slow (r.d.s.) (2 o cation) fast (major) Step 1 Step 2 h. 8-18

4 xamples (1) l l l (95 : 5) (2) h (98 : 2) h Modern Statement of Markovnikov s ule xamples In the ionic addition of an unsymmetrical reagent to a double bond, the positive portion of the added reagent attaches itself to a carbon atom of the double bond so as to yield the more stable carbocation as an intermediate (1) l l more stable 3 o cation l (major) l l h less stable 1 o cation (minor) h xamples 2. egioselective eactions (2) I l I more stable 3 o cation l l (major) I When a reaction that can potentially yield two or more constitutional isomers actually produces only one (or a predominance of one), the reaction is said to be regioselective l l l l (major) l (minor) I less stable 1 o cation I (minor) h egioselectivity: regioisomers 95 : 5 h. 8-24

5 2D. An xception to Markovnikov s ule heat (anti-markovnikov's product) Via a radical mechanism (see hapter 10) This anti-markovnikov addition does not take place with I, l, and F, even when peroxides are present h Stereochemistry of the Ionic Addition to an Alkene u attack from top u achiral trigonal planar carbocation 3 u (S)-2-alohexane (50%) 2 attack from bottom u 3 racem mate ()-2-alohexane (50%) h Addition of Sulfuric Acid to Alkenes S conc. 2 S 4 cold Addition of S 3 across a = bond more stable 3 o cation S 3 S 3 less stable 1 o cation h A. Alcohols from Alkyl ydrogen Sulfates conc. 2 S 4 cold S 3 2 heat The overall result of the addition of sulfuric acid to an alkene followed by hydrolysis is the Markovnikov addition of and h Addition of Water to Alkenes: Acid-atalyzed ydration verall process Addition of across a = bond is the electrophile Follow Markovnikov s rule 2 dilute 3 (e.g. dilute 2 S 4, 3 P 4 ) h A. Mechanism slow (step 1) more stable 3 o cation 2 fast (step 2) fast (step 3) 2 h. 8-30

6 5. earrangements earrangement can occur with certain carbocations NT 2 2 S 4 (major product) 2 1,2-alkyl shift h Alcohols from Alkenes through xymercuration Demercuration: Markovnikov Addition Step 1: xymercuration g(ac) 2 TF- 2 Step 2: Demercuration gac Na 4 gac h A. egioselectivity of xymercura- tion Demercuration xymercuration demercuration is also highly regioselective and follows Markovnikov s rule g(ac) 2 TF- 2 gac Na 4 6. earrangements Seldom ccur in xymercuration Demercuration ecall: acid-catalyzed hydration of some alkenes leads to rearrangement products e.g. 2 2 S 4 h h S 4 2 1,2-alkyl shift earrangements of the carbon skeleton seldom occur in oxymercuration demercuration no rearrangement 1. g(ac) 2, TF Na 4 2 via h g(ac) h. 8-36

7 6. Mechanism of xymercuration Does not undergo a free carbocation Ac g Ac Ac gac 2 Stereochemistry Usually anti-addition 3 g(ac) 2 TF g(ac) gac gac 2 h g(ac) h Although attack by water on the bridged mercurinium ion leads to anti addition of the hydroxyl and mercury groups, the reaction that replaces mercury with hydrogen is not stereocontrolled (it likely involves radicals). This step scrambles the overall stereochemistry The net result of oxymercuration demercuration is a mixture of syn and anti addition of and to the alkene h Solvomercuration-Demercuration g( 2 F 3 ) 2 TF- g( 2 F 3 ) Na 4 h Alcohols from Alkenes through ydroboration xidation: Anti-Markovnikov Syn ydration " 3 " 2 Addition of 2 across a = bond 3 exists as dimer 2 6 or complex with coordinative solvent ( 3 -TF) S ( 3 -DMS) Me Me h h. 8-42

8 1. 3 -TF syn addition ompare with oxymercurationdemercuration 3 g(ac) 2 TF- 2 3 g(ac) , 3 anti addition Na 4 Anti-Markovnikov addition of & h Markovnikov addition of & 3 h ydroboration: Synthesis of Alkylboranes alkene boron hydride hydroboration alkylborane h A. Mechanism of ydroboration 3 3 syn addition of and 3 π complex four-atom concerted T.S. 3 3 h ther examples 8. Stereochemistry of ydroboration (1) 2 -TF 2 2 Syn addition (99 : 1) 2 (2) 2 -TF 3 3 -TF (98 : 2) h h. 8-48

9 9. xidation and ydrolysis of Alkylboranes xidation always ends up on the least hindered carbon (trialkyl borane) h h Via ydrolysis 3 Na 2 3 Na 3 3 h h verall synthetic process of hydroboration-oxidation-hydrolysis xample anti-markovnikov syn addition TF 3 -TF Na, verall: anti-markovnikov addition of across a = bond pposite regioisomers as oxymercuration-demercuration h This oxidation step occurs with retention of configuration 2 2 h. 8-54

10 10. Summary of Alkene ydration Methods Summary of Methods for onverting Alkene to Alcohol eaction egiochemistry Stereochemistry Acid-catalyzed hydration Markovnikov addition Markovnikov addition Anti-Markovnikov addition Not controlled Not controlled Stereospecific: syn addition of and ccurrence of earrangements Frequent Seldom Seldom h xamples 2 via 1. g(ac) 2, TF Na 4, 1,2-hydride shift with rearrangement Markovnikov addition of 2 without rearrangement TF , xymercurationdemercuration ydroborationoxidation anti-markovnikov, syn addition of 2 h Protonolysis of Alkylboranes e.g. 3 2 heat 3 2 alkylborane alkane TF D 3 D enantiomer Protonolysis of an alkylborane takes place with retention of configuration; hydrogen replaces boron where it stands in the alkylborane verall stereochemistry of hydroboration protonolysis: syn h via 3 2 h lectrophilic Addition of omine and hlorine to Alkenes Addition of ( = l, ) across a = bond 2 l 4 (vicinal dibromide) h xamples (1) 2 5 o (anti addition of 2 ) (racemate) l (2) l o 1 (anti addition of l 2 ) l same as l l (rotation of 1-2 bond) h. 8-60

11 12A. Mechanism of alogen Addition Stereochemistry Anti addition bond becomes polarized when close to alkene l 4 (vincinal Dibromide) (bromonium) h enantiomer (anti) S N 2 reaction h Stereospecific eactions A reaction is stereospecific when a particular stereoisomeric form of the starting material reacts by a mechanism that gives a specific stereoisomeric form of the product h eaction l 4 trans-2-utene eaction l 4 cis-2-utene (2,3S)-2,3-Dibromobutane (a meso compound) (2,3) (a pair of enantiomers) h (2S,3S) 3 Addition of bromine to cis-2-utene 3 3 (a) 3 3 (a) (b) (2,3)-2,3-Dibromobutane (chiral) 3 3 bromonium ion (achiral) 3 (b) 3 (2S,3S)-2,3-Dibromobutane (chiral) h Addition of bromine to trans-2-utene (a) 3 (a) (b) (,S)-2,3-Dibromobutane (meso) 3 3 bromonium ion (achiral) 3 (b) 3 (,S)-2,3-Dibromobutane (meso) h. 8-66

12 14. alohydrin Formation Mechanism Addition of and ( = l, ) across a = bond is the electrophile Follow Markovnikov s rule 3 3 h h ther variation If 2 is replaced by, Ö will be the nucleophile e.g. 2 Me Me 15. Divalent arbon ompounds: arbenes 15A. Structure and eactions of Methylene heat 2 N N 2 N N or light Diazomethane Methylene (a carbene) Nitrogen h h N N I 2 N N 2 N N II III 15. eactions of ther arbenes: Dihalocarbenes : 2 (e.g. :l 2 ) Generation by α-elimination of chloroform 2 Alkene Methylene yclopropane l l l t u l 2 t u l h h. 8-72

13 Usually a syn (cis) addition across a = bond t uk l 3 l l (a cyclopropane) Stereospecific reactions l 2 l 2 l l l l h h arbenoids: The Simmons-Smith Smith yclopropane Synthesis A stereospecific syn (cis) addition across a = bond 2 I 2 2 I 2 Zn(u) (Zinc-copper couple) I ZnI 2 (a carbenoid) (trans) Zn(u) 2 I 2 (trans) Zn(u) (cis) (cis) h h xidation of Alkenes: Syn 1,2-Dihydroxylation verall: addition of 2 groups across a = bond 16A. Mechanism for Syn Dihydroxylation of Alkenes dil. KMn 4, 2 cold Mn 2 Mn 2 eagents: dilute KMn 4 / / 2 / cold or s 4, pyridine then NaS 3, 2 h s 4 pyridine s NaS 3 2 s h. 8-78

14 oth reagents give syn dihydroxylation dil. KMn 4, 2, cold or s 4, pyridine then NaS 3 (cis-diol) h omparison of the two reagents KMn 4 : usually lower yield and possibly side products due to overoxidation 1. KMn 4, 2. (oxidative cleavage of =) s 4 : usually much higher yield but s 4 is extremely toxic h xidative leavage of Alkenes ther examples 17A. leavage with ot asic Potassium Permanganate KMn 4, a, 2 b b 2 a a b b a or a b 3 2 b a h (1) (2) 1. KMn 4,, 2, heat KMn 4,, 2, heat 2. 3 h leavage with zone xamples ' " Zn, Ac ' or Me 2 S " (1) Zn, Ac (2) Me 2 S h h. 8-84

15 Mechanism initial ozonide 18. lectrophilic Addition of omine & hlorine to Alkynes 2 (excess) 2 l 2 ( = l,, I) Zn(Ac) 2 ozonide h (anti-addition) h Addition of ydrogen alides to Alkynes (excess) ( = l,, I) egioselectivity Follow Markovnikov s rule gem-dibromide h Mechanism h Anti-Markovnikov addition of hydrogen bromide to alkynes occurs when peroxides are present in the reaction mixture peroxides () and (Z) (74%) 20. xidative leavage of Alkynes 1. 3 ' 2 ' 2 2. Ac 1. KMn 4, ' ' xample Ac h h. 8-90

16 21. ow to Plan a Synthesis: Some Approaches & xamples In planning a synthesis we often have to consider four interrelated aspects: 1. onstruction of the carbon skeleton 2. Functional group interconversions 3. ontrol of regiochemistry 4. ontrol of stereochemistry 21A. etrosynthetic Analysis ow to synthesize? etrosynthetic analysis (target molecule) (precursor) h h Synthesis 2 Markovnikov addition of 2 ow to synthesize? etrosynthetic analysis (target molecule) (precursor) or 1. g(ac) 2, TF Na 4, Synthesis TF , h anti-markovnikov addition of 2 h Disconnections, Synthons, and Synthetic quivalents ne approach to retrosynthetic analysis is to consider a retrosynthetic step as a disconnection of one of the bonds In general, we call the fragments of a hypothetical retrosynthetic disconnection Synthons h xample ow? etrosynthetic analysis (i) (gem-dibromide came from addition of across a bond) h. 8-96

17 etrosynthetic analysis Synthesis synthons (ii) 3 3 NaN 2 liq. N 3-30 o 3 Na I disconnection (via an S N 2 reaction) 3 I Na synthetic equivalent 3 (excess) 3 h h Stereochemical onsiderations 3 3 ow? 3 3 h etrosynthetic analysis The precursor of a vicinal dibromide is usually an alkene omination of alkenes are anti addition 3 3 (rotate 180 o ) (anti addition of 2 ) 3 3 (anti addition of 2 ) 3 h Synthesis 1. Li, liq. N N 4 l (anti addition of 2 ) 2 /l 4 same 3 as 3 (anti addition of 2 ) ND F APT 8 h h