hapter 8 Alkenes and Alkynes II: Addition Reactions h. 8-1
1. Addition Reactions of Alkenes E + E Nu Nu h. 8-2
1A. ow To Understand Additions to Alkenes This is an addition reaction: E Nu added across the double bond E + E Nu Nu π-bond σ-bond 2 σ-bonds Bonds broken Bonds formed h. 8-3
Since p bonds are formed from the overlapping of π orbitals, π electron clouds are above and below the plane of the double bond π electron clouds h. 8-4
Electrophilic electron seeking = and π bonds are particularly susceptible to electrophilic reagents (electrophiles) ommon electrophile +, X + (X = l,, I), g 2+, etc. h. 8-5
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 B to form a σ bond provides an addition product h. 8-6
δ + E δ Nu E + Nu Nu E h. 8-7
2. Electrophilic Addition of ydrogen alides to Alkenes: Mechanism and Markovnikov s Rule Mechanism δ + E δ Nu A Nu Nu E h. 8-8
Mechanism Sometimes do not go through a free carbocation, may go via E h. 8-9
Markovnikov s Rule For symmetrical substrates, no problem for regiochemistry E E E Nu same as Nu E Nu same as Nu E h. 8-10
Markovnikov s Rule But for unsymmetrical substrates, two regioisomers are possible 3 E Nu 3 E or 3 E Nu Nu 3 E Nu different from 3 Nu E h. 8-11
Markovnikov s Rule 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 h. 8-12
Markovnikov s Rule Thus δ + E δ Nu E Nu E NOT E Note: carbocation stability 3 o > 2 o > 1 o h. 8-13
Addition of ydrogen alides Addition of l, and I across a = bond + is the electrophile + δ + δ slow r.d.s fast NO h. 8-14
h. 8-15
2A. Theoretical Explanation of Markovnikov s Rule 3 δ + δ X 3 step 1 (slow r.d.s.) 2 o carbocation (more stable) or 3 1 o carbocation (more stable) One way to state Markovnikov s rule is to say that in the addition of X 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. 8-16
(1 o cation) fast (minor) slow (r.d.s.) (2 o cation) fast (major) Step 1 Step 2 h. 8-17
h. 8-18
Examples (1) l l + l (95 : 5) (2) + (98 : 2) h. 8-19
2B. Modern Statement of Markovnikov s Rule 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 h. 8-20
Examples O O l l (1) δ + l δ O more stable 3 o cation (major) l O l O less stable 1 o cation (minor) h. 8-21
Examples l I I (2) δ + I δ l more stable 3 o cation l (major) I less stable 1 o cation l l I (minor) h. 8-22
2. Regioselective Reactions 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 (major) + l (minor) Regioselectivity: regioisomers 95 : 5 h. 8-23
2D. An Exception to Markovnikov s Rule RO OR 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. 8-24
3. Stereochemistry of the Ionic Bu Addition to an Alkene attack from top X Bu achiral trigonal planar carbocation X X 3 Bu (S)-2-alohexane (50%) 2 X attack from bottom Bu 3 X (R)-2-alohexane (50%) racemate h. 8-25
4. Addition of Sulfuric Acid to Alkenes O O S O δ O δ + conc. 2 SO 4 cold Addition of OSO 3 across a = bond more stable 3 o cation OSO 3 OSO 3 less stable 1 o cation h. 8-26
4A. Alcohols from Alkyl ydrogen Sulfates conc. 2 SO 4 OSO 3 2 O O cold heat The overall result of the addition of sulfuric acid to an alkene followed by hydrolysis is the Markovnikov addition of and O h. 8-27
5. Addition of Water to Alkenes: Acid-atalyzed ydration Overall process Addition of O across a = bond + is the electrophile Follow Markovnikov s rule 2 O dilute 3 O + (e.g. dilute 2 SO 4, 3 PO 4 ) O h. 8-28
5A. Mechanism O 2 O slow fast (step 1) more stable (step 2) O 3 o cation fast (step 3) 2 O O + O h. 8-29
5B. Rearrangements Rearrangement can occur with certain carbocations 2 O 2 SO 4 NOT O O 2 O 1,2-alkyl shift (major product) h. 8-30
6. Alcohols from Alkenes through Oxymercuration Demercuration: Markovnikov Addition Step 1: Oxymercuration g(oac) 2 TF- 2 O O goac Step 2: Demercuration O goac NaB 4 O O h. 8-31
6A. Regioselectivity of Oxymercuration Demercuration Oxymercuration demercuration is also highly regioselective and follows Markovnikov s rule g(oac) 2 TF- 2 O O goac NaB 4 O O h. 8-32
6B. Rearrangements Seldom Occur in Oxymercuration Demercuration Recall: acid-catalyzed hydration of some alkenes leads to rearrangement products e.g. 2 O 2 SO 4 O h. 8-33
2 O 2 SO 4 1,2-alkyl shift O 2 O 2 O O h. 8-34
Rearrangements of the carbon skeleton seldom occur in oxymercuration demercuration no rearrangement O 1. g(oac) 2, TF- 2 O 2. NaB 4 via O g(oac) h. 8-35
6. Mechanism of Oxymercuration Does not undergo a free carbocation δ + g δ OAc OAc AcO + δ + δ + goac 2 O goac goac O 2 O O h. 8-36
Stereochemistry Usually anti-addition 2 O g(oac) 2 δ + 3 TF- 2 O 3 δ + g(oac) O 3 g(oac) h. 8-37
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 O to the alkene h. 8-38
Solvomercuration-Demercuration g(o 2 F 3 ) 2 OR TF-RO g(o 2 F 3 ) NaB 4 O OR h. 8-39
7. Alcohols from Alkenes through ydroboration Oxidation: Anti-Markovnikov Syn ydration "B 3 " B 2 Addition of B 2 across a = bond h. 8-40
B 3 exists as dimer B 2 6 or complex with coordinative solvent B B Me B O B S Me (B 3 -TF) (B 3 -DMS) h. 8-41
syn addition 1. B 3 -TF O 3 2. 2 O 2, O 3 Anti-Markovnikov addition of & O h. 8-42
ompare with oxymercurationdemercuration O g(oac) 2 3 TF- 2 O 3 g(oac) anti addition NaB 4 O Markovnikov addition of & O 3 h. 8-43
8. ydroboration: Synthesis of Alkylboranes + B hydroboration B alkene boron hydride alkylborane h. 8-44
8A. Mechanism of ydroboration 3 3 3 + B B π complex B 3 syn addition of and B B four-atom concerted T.S. 3 δ + δ B h. 8-45
Other examples (1) B 2 -TF + B 2 2 B (99 : 1) (2) B 2 -TF + B 2 2 B (98 : 2) h. 8-46
8B. Stereochemistry of ydroboration Syn addition B 2 3 B 3 -TF 3 h. 8-47
9. Oxidation and ydrolysis of Alkylboranes δ + B δ B 2 B B always ends up on the least hindered carbon B B (trialkyl borane) h. 8-48
Oxidation B 2 O 2 O O B O h. 8-49
Via R 3 B O O R R B O O R R R B OR O O R RO B OR R R B O OR O O O R OR O O B OR OR RO B OR h. 8-50
ydrolysis O O B O NaO 2 O 3 O + Na 3 BO 3 h. 8-51
Overall synthetic process of hydroboration-oxidation-hydrolysis 1. B 3 -TF 2. 2 O 2 3. NaO, 2 O O Overall: anti-markovnikov addition of O across a = bond Opposite regioisomers as oxymercuration-demercuration h. 8-52
Example anti-markovnikov syn addition B 3 -TF B 2 3 3 O 2 O 2 O 3 This oxidation step occurs with retention of configuration h. 8-53
10. Summary of Alkene ydration Methods Summary of Methods for onverting Alkene to Alcohol Reaction Regiochemistry Stereochemistry Acid-catalyzed hydration Markovnikov addition Not controlled Occurrence of Rearrangements Frequent Oxymercurationdemercuration Markovnikov addition Not controlled Seldom ydroborationoxidation Anti-Markovnikov addition Stereospecific: syn addition of and O Seldom h. 8-54
Examples via 1,2-hydride shift + 2 O O 1. g(oac) 2, TF- 2 O 2. NaB 4, O with rearrangement O Markovnikov addition of 2 O without rearrangement 1. B 3 -TF 2. 2 O 2, O O anti-markovnikov, syn addition of 2 O h. 8-55
11. Protonolysis of Alkylboranes 3 O 2 R B R + 3 O 2 B heat alkylborane alkane Protonolysis of an alkylborane takes place with retention of configuration; hydrogen replaces boron where it stands in the alkylborane Overall stereochemistry of hydroboration protonolysis: syn h. 8-56
e.g. 1. B 3 -TF 3 2. 3 O 2 D 3 D + enantiomer via 3 B 2 h. 8-57
12. Electrophilic Addition of omine and hlorine to Alkenes Addition of X X (X = l, ) across a = bond 2 l 4 (vicinal dibromide) h. 8-58
Examples (1) 2 5 o + (anti addition of 2 ) (racemate) l 2 (2) Ph Ph Ph 10 o (anti addition of l 2 ) 1 l l 2 Ph Ph Ph same as l l (rotation of 1-2 bond) h. 8-59
12A. Mechanism of alogen Addition + bond becomes polarized when close to alkene δ + δ (vincinal Dibromide) (bromonium) + h. 8-60
Stereochemistry Anti addition l 4 S N 2 reaction enantiomer + (anti) h. 8-61
13. Stereospecific Reactions 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. 8-62
Reaction 1 3 3 2 l 4 3 3 3 3 trans-2-butene (2R,3S)-2,3-Dibromobutane (a meso compound) Reaction 2 3 3 2 l 4 3 3 + 3 3 cis-2-butene (2R,3R) (2S,3S) (a pair of enantiomers) h. 8-63
Addition of bromine to cis-2-butene 3 δ + δ 3 3 (a) bromonium ion (achiral) (a) 3 3 (b) (2R,3R)-2,3-Dibromobutane (chiral) 3 3 (b) 3 (2S,3S)-2,3-Dibromobutane (chiral) h. 8-64
Addition of bromine to trans-2-butene 3 δ + δ 3 3 (a) bromonium ion (achiral) 3 (a) 3 (b) (R,S)-2,3-Dibromobutane (meso) 3 3 (b) 3 (R,S)-2,3-Dibromobutane (meso) h. 8-65
14. alohydrin Formation X 2 2 O O X Addition of O and X (X = l, ) across a = bond X + is the electrophile Follow Markovnikov s rule h. 8-66
Mechanism δ + 2 O 3 2 O 3 δ + O 3 3 h. 8-67
Other variation If 2 O is replaced by RO, RÖ will be the nucleophile e.g. 2 OMe MeO h. 8-68
15. Divalent arbon ompounds: arbenes 15A. Structure and Reactions of Methylene heat 2 N N 2 + N N or light Diazomethane Methylene (a carbene) Nitrogen h. 8-69
2 N N 2 N N 2 N N I II III + 2 Alkene Methylene yclopropane h. 8-70
15B. Reactions of Other arbenes: Dihalocarbenes :X 2 (e.g. :l 2 ) Generation by α-elimination of chloroform l l l O t Bu l 2 + t BuO + l h. 8-71
Usually a syn (cis) addition across a = bond t BuOK l 3 l l (a cyclopropane) h. 8-72
Stereospecific reactions l 2 l l l 2 l l h. 8-73
15. arbenoids: The Simmons-Smith yclopropane Synthesis 2 I 2 + Zn(u) (Zinc-copper couple) I ZnI 2 (a carbenoid) h. 8-74
A stereospecific syn (cis) addition across a = bond 2 I 2 (trans) Zn(u) (trans) 2 I 2 Zn(u) (cis) (cis) h. 8-75
16. Oxidation of Alkenes: Syn 1,2-Dihydroxylation Overall: addition of 2 O groups across a = bond O O Reagents: dilute KMnO 4 / O / 2 O / cold or OsO 4, pyridine then NaSO 3, 2 O h. 8-76
16A. Mechanism for Syn Dihydroxylation of Alkenes dil. KMnO 4 O, 2 O cold O O Mn O O O 2 O O O + MnO 2 OsO 4 pyridine O O Os O O NaSO 3 2 O O O + Os h. 8-77
Both reagents give syn dihydroxylation dil. KMnO 4 O, 2 O, cold or OsO 4, pyridine then NaSO 3 O O (cis-diol) h. 8-78
omparison of the two reagents KMnO 4 : usually lower yield and possibly side products due to overoxidation 1. KMnO 4, 2. + O + O O (oxidative cleavage of =) O OsO 4 : usually much higher yield but OsO 4 is extremely toxic h. 8-79
17. Oxidative leavage of Alkenes 17A. leavage with ot Basic Potassium Permanganate KMnO 4, O O a, 2 O b b 2 a a b or 3 O + O b a a b 2 b O a O h. 8-80
Other examples (1) 1. KMnO 4, O, 2 O, heat 2. 3 O + O + O O (2) 1. KMnO 4, O, 2 O, heat 2. 3 O + O O O h. 8-81
17B. leavage with Ozone R R" R R" R' 1. O 3 O + 2. Zn, AcO R' or Me 2 S O h. 8-82
Examples O (1) 1. O 3 2. Zn, AcO O (2) 1. O 3 2. Me 2 S + O O h. 8-83
Mechanism + O O O O O O initial ozonide O O O O O Zn(OAc) 2 + O O O O ozonide O + O h. 8-84
18. Electrophilic Addition of omine & hlorine to Alkynes R X 2 (excess) 2 l 2 (X = l,, I) R X X X X R X 2 X X2 R X X X X X (anti-addition) h. 8-85
19. Addition of ydrogen alides to Alkynes X (excess) R (X = l,, I) Regioselectivity Follow Markovnikov s rule X R X 3 3 3 gem-dibromide h. 8-86
Mechanism 3 3 3 3 3 h. 8-87
Anti-Markovnikov addition of hydrogen bromide to alkynes occurs when peroxides are present in the reaction mixture peroxides (E) and (Z) (74%) h. 8-88
20. Oxidative leavage of Alkynes 1. O 3 R R' RO 2 + R'O 2 2. OAc OR 1. KMnO 4, O R R' + R'O 2 2. 3 O + RO 2 Example 1. O 3 Ph 3 PhO 2 + 3 O 2 2. AcO h. 8-89
21. ow to Plan a Synthesis: Some Approaches & Examples 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 h. 8-90
21A. Retrosynthetic Analysis ow to synthesize? O Retrosynthetic analysis O (target molecule) (precursor) h. 8-91
Synthesis Markovnikov addition of 2 O + 2 O O or 1. g(oac) 2, TF- 2 O 2. NaB 4, O h. 8-92
ow to synthesize? Retrosynthetic analysis O O (target molecule) (precursor) Synthesis 1. B 3 -TF 2. 2 O 2, O anti-markovnikov addition of 2 O O h. 8-93
21B. Disconnections, Synthons, and Synthetic Equivalents One 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. 8-94
Example Ph ow? Ph 3 Retrosynthetic analysis (i) Ph 3 Ph 3 (gem-dibromide came from addition of across a bond) h. 8-95
Retrosynthetic analysis synthons (ii) Ph 3 Ph + 3 disconnection 3 I + Ph Na synthetic equivalent h. 8-96
Synthesis Ph NaN 2 liq. N 3 Ph Na -30 o 3 I (via an S N 2 reaction) Ph 3 (excess) Ph 3 h. 8-97
21. Stereochemical onsiderations 3 3 ow? 3 3 h. 8-98
Retrosynthetic analysis 3 The precursor of a vicinal dibromide is usually an alkene omination of alkenes are anti addition 3 (rotate 180 o ) 3 3 (anti addition of 2 ) 3 3 3 (anti addition of 2 ) 3 h. 8-99
Synthesis 3 3 2. N 4 l 1. Li, liq. N 3 3 3 (anti addition of 2 ) 3 3 same as 3 2 /l 4 3 (anti addition of 2 ) h. 8-100
END OF APTER 8 h. 8-101