1. Chapter 4. Electrophilic Additions
Advanced Org Chem-Carey B
Fall 2002
Chapter 4. Electrophilic Additions
regioselective
non-stereoselective
regioselective
stereoselective
regioselective
stereoselective
Carey B-Chap 4-5ed
Chapter 4

2. Addition of Hydrogen Halides: HX
Advanced Org Chem-Carey B
Fall 2002
Addition of Hydrogen Halides: HX
Markovnikov’s rule: regioselectivity;  290 top
more stable at more substituted C:  290 middle
slower reaction for mono/disubstituted alkenes: addition of silica or alumina in CH2Cl2 to SOCl2 or (COCl)2
in situ generation of HCl: TMSCl & H2O;  291 top
rearrangements & solvent participation:  291 middle
stereochemistry: depends on stability of carbocations
anti: 2-butenes, 1-Me-cyclopentene ( 291 bottom)
syn: conjugated alkenes & reaction conditions
 292 Table 4.1 entries 1 & 10
Carey B-Chap 4-5ed
Chapter 4

3. General Mechanism of Polar Addition
Advanced Org Chem-Carey B
Fall 2002
General Mechanism of Polar Addition
free carbocation: AdE2
syn/rac
ion-pair: AdE2
simultaneous: AdE3
anti
 292 middle
Carey B-Chap 4-5ed
Chapter 4

4. Addition of H2O & Oxygen Nucleophiles
Advanced Org Chem-Carey B
Fall 2002
Addition of H2O & Oxygen Nucleophiles
Hydration: addition of H2O with strong acids
good for 3o alcohols: Markownikoff’s rule;  293 top
Addition of ROH & RCO2H:  293 bottom
in the presence of strong acids: HBF4
TFA: acid-catalyst & addition
Not much synthetic utility due to strongly acidic conditions and rearrangement products
Carey B-Chap 4-5ed
Chapter 4

5. Oxymercuration: Addition of OH & Hg+
Advanced Org Chem-Carey B
Fall 2002
Oxymercuration: Addition of OH & Hg+
Mild conditions & less rearrangements
mercurinium ion: Markownikoff’s rule;  294 bottom
nucleophiles: oxygen/nitrogen;  299 Scheme 4.1
demercuration: reductive cleavage;  295 top
NaBH4: free-radical intermediate;  295 middle
Na(Hg) in protic solvents: retention;  295 middle
reactivity of alkenes:  296 middle
stereochemistry: anti addition;  296 bottom
allylic strain & directing effect:  296 bottom
neighboring-group participation:  297 middle
Carey B-Chap 4-5ed
Chapter 4

6. Addition of Halogens: X2 (I)
Advanced Org Chem-Carey B
Fall 2002
Addition of Halogens: X2 (I)
Bridged halonium ions: anti addition;  298 bot
syn addition: a Ph substituent;  300 top
Cl2: similar to Br2 but more syn products;  300 bot
carbocation intermediates:  301 top
synthesis of halohydrins: in aq. DMSO;  302 middle
in-situ generation of HOX: HOd-Xd+;  303 top
mild halogen sources: NBS/NCS, pyr•HBr3, R4N+Br3-, dioxane-Br2, tetrabromocyclohexadienone ( 304 bot), NIS, [pyr-I-pyr]+BF4-, [coll-I-coll]+PF6-;  305 Table 4.2
Carey B-Chap 4-5ed
Chapter 4

7. Addition of Halogens: X2 (II)
Advanced Org Chem-Carey B
Fall 2002
Addition of Halogens: X2 (II)
Addition of F2: highly reactive & ionic intermed.
nearly no selectivity: in favor of syn;  303 middle
other fluorinating reagents:  303 bot & 304 top
Iodination: not useful;  304 middle
Other reagents: X+-Y-;  306 Scheme 4.2
similar mechanism to halogenation: halonium bridged (symmetric/unsymmetrical) cationic intermediates
Markovnikov regioselectivity
anti stereoselectivity due to the bridged intermediates
Carey B-Chap 4-5ed
Chapter 4

8. Addition of Sulfur & Selenium
Advanced Org Chem-Carey B
Fall 2002
Addition of Sulfur & Selenium
Electrophilic S & Se agents:  308 Scheme 4.3
bridged intermediates: S & Se;  307 middle
anti-Markownikoff regioselectivity: more stronger C-S bonds & less electrophilic sulfurane;  310 top
anti stereoselectivity: neither rearrangement nor syn
rearrangement possible with LiClO4
addition of RSeX: anti-Markownikoff but equilibration
selenylation with external Nu;  309 bot – 310 top
Carey B-Chap 4-5ed
Chapter 4

9. Electrophilic Cyclization
Advanced Org Chem-Carey B
Fall 2002
Electrophilic Cyclization
Baldwin’s rule:  311 top
preferred: 5-exo over 6-endo; 5-endo over 4-exo
Iodocyclization reactions:  Scheme 4.4
good electrophiles with intramolecular nucleophiles
cyclization under basic conditions: kinetic, anti & exo
thermodynamic control: no base;  313 top
depending on conformations:  313 bot &  314 top
other Nu & further reactions:  315 top
amides:  316 middle & bottom
Cyclization with Other electrophiles: Se/S/Hg
 Scheme 4.5 &  327 Scheme 4.6
Carey B-Chap 4-5ed
Chapter 4

10. Electrophilic Substitution at a-C to Carbonyls
Advanced Org Chem-Carey B
Fall 2002
Electrophilic Substitution at a-C to Carbonyls
a-Halogenation of ketones:  329 bottom
electrophilic addition of enols/enolates:  328 bottom
monohalogenation: CuBr2/CuCl2;  330 top
polyhalogenation: haloform reactions;  329 top
a-fluoroketones: 1-F-4-OH-DABCO;  331 top
halogenation of reactive enols:  330 middle
a-Halogenation of carboxylic acids:  331 mid
Hell-Volhard-Zelinsky reaction: P(red) & Br2
a-Substitution of S & Se:  332 Scheme 4.7
facile elimination of oxides: a,b-unsaturated carbonyls
Carey B-Chap 4-5ed
Chapter 4

11. Addition to Allenes & Alkynes
Advanced Org Chem-Carey B
Fall 2002
Addition to Allenes & Alkynes
Allenes: addition to terminal C;  333 bottom
internal C: less stable due to orthogonal p orbitals
HX: protonation at the terminal carbon;  334 middle
protonation at the sp carbon: Ph, 1,1-diMe;  334 mid
Alkynes: less reactive than alkenes
10 kcal/mol less stable vinyl cations than alkyl cations
HBr: anti & Markownikoff selectivity:  335 top
rate & selectivity increase with R4N+Br- in TFA:CH2Cl2
HCl: syn (kinetic) to anti (thermodynamic);  335 mid
Carey B-Chap 4-5ed
Chapter 4

12. Advanced Org Chem-Carey B
Fall 2002
Addition to Alkynes
Addition of Cl2: depends on the substrate
in AcOH: syn to 1-pentyne/hexyne & anti to 2/3-butyne
vinyl cation vs cyclic chloronium ion:  336 bottom
addition of Br2: vinyl cation vs cyclic bromonium ion
Addition of H2O: equivalent to -C(O)CH2-
addition of AcOH:  335 middle
Hg2+-catalyzed hydration:  336 Scheme 4.8
Addition of RSeY: anti,  337 top
aryl alkynes: regioselective than alkyl alkynes
Carey B-Chap 4-5ed
Chapter 4

13. Hydroboration: Addition of H-BR2
Advanced Org Chem-Carey B
Fall 2002
Hydroboration: Addition of H-BR2
Electrophilic BR3: (BH3)2;  337 middle
Regioselectivity:  338 Table 4.3
B to the less substituted carbon: R2Bd+–Hd- (r = -0.5)
alkylboranes: more selective;  338 middle &  339 top
Stereoselectivity: syn & concerted;  339 mid
Reversibility: to the terminal isomer;  343 bot
intramolecular mechanism possible:  343 bottom
facile migration with bulky boranes:  343 middle
Carey B-Chap 4-5ed
Chapter 4

14. Stereoselectivity of Boranes
Advanced Org Chem-Carey B
Fall 2002
Stereoselectivity of Boranes
Carey B-Chap 4-5ed
Chapter 4

15. Other Hydroboration Reagents
Advanced Org Chem-Carey B
Fall 2002
Other Hydroboration Reagents
Haloboranes: ClBH2, BrBH2, Cl2BH, Br2BH
more regioselective & similar reactivity to (BH3)2
further transformations possible:  340 top
Oxygenated boranes: less reactive but selective
catecholborane & pinacolborane:  340 bottom
activated by additives: 10-20% of DMA in CH2Cl2
catalytic activation: Wilkinson’s catalyst [ClRh(PPh3)3]
metal-catalyzed hydroboration:  341 top
selectivity: depends on metals;  341 middle & bottom
Carey B-Chap 4-5ed
Chapter 4

16. Useful Hydroboration Reagents
Advanced Org Chem-Carey B
Fall 2002
Useful Hydroboration Reagents
Carey B-Chap 4-5ed
Chapter 4

17. Reactions of Organoboranes (I)
Advanced Org Chem-Carey B
Fall 2002
Reactions of Organoboranes (I)
Conversion into alcohols:  344 bottom
concerted migration: retention;  348 Scheme 4.9
anti-Markownikoff regioselectivity: entries 1-4
other oxidants: H2O2 & NaOH, O2, Na2CO4, R3N+-O-
migratory aptitude: 3o > 2o > 1o carbon
Reactions to ketones/aldehydes:  345 top
other oxidants: PCC, TPAP & R3N+-O-; entries 5-7
to carboxylic acids: terminal alkenes;  345 middle
Carey B-Chap 4-5ed
Chapter 4

18. Transformation of Boranes: Alcohols (I)
Advanced Org Chem-Carey B
Fall 2002
Transformation of Boranes: Alcohols (I)
Carey B-Chap 4-5ed
Chapter 4

19. Reactions of Organoboranes (II)
Advanced Org Chem-Carey B
Fall 2002
Reactions of Organoboranes (II)
Conversion into amines: concerted mechanism
H2N-Cl/-OSO3H: 1o amines;  345 bottom
R’-N3 & RBCl2: 2o amines;  346 top
2o amines: Cl-NHR’ & R3B;  346 middle
Transformation into halides:  346 bottom
reactive with base & halogen: Br2 & NaOMe
Reactions with CO: depending on the conditions
3o/2o/1o alcohols, ketones/aldehydes
Carey B-Chap 4-5ed
Chapter 4

20. Reactions with CO (I): General
Advanced Org Chem-Carey B
Fall 2002
Reactions with CO (I): General
Carey B-Chap 4-5ed
Chapter 4

21. Enantioselective Hydroboration
Advanced Org Chem-Carey B
Fall 2002
Enantioselective Hydroboration
Chiral boranes: from terpenes;  347 bottom
terpenes: both enantiomers, low but >99% ee purity
Enantioselection with (Ipc)2BH:  349 bottom
Z-1,2-alkenes: 75-90% ee; E-1,2-alkenes: 5-30% ee
with IpcBH2 & recycle of a-pinene:  350 middle
syntheses of chiral alcohols and amines:  351 mid
transition metal for enantioselectivity:  342 bottom
Carey B-Chap 4-5ed
Chapter 4

22. Hydroboration of Alkynes
Advanced Org Chem-Carey B
Fall 2002
Hydroboration of Alkynes
syn Addition to alkynes: Z-dialkylalkenes
Reactive with (BH3)2: polymeric byproducts
use of R2BH: catecholborane; syn,  352 top
anti addition of HBr to alkynes: Br2;  352 middle
Br2BH•SMe2 & pinacolborane: E-iodide;  352 bottom
from catecholboranes & I2:  239 bottom
9-BBN for internal alkynes: Z-alkenes;  353 top
Carey B-Chap 4-5ed
Chapter 4

23. Carbo(Hydro)metallation: Al, Zr
Advanced Org Chem-Carey B
Fall 2002
Carbo(Hydro)metallation: Al, Zr
R(H)AlR2: less reactive than boranes
terminal/strained alkenes & alkynes:  353 bottom
less electronegative Al: [-CH3] in Me3Al vs [+CH3] in Me3B
effective catalyst: [(Cp)2ZrX2];  355 bottom
enantioselectivity & activation:  356 top &  357 bottom
functionalization of intermediates:  356 Scheme 4.10
HZrCl(Cp)2: Cl2Zr(Cp)2 & M-H;  357 top
internal alkynes: equilibration to the less hindered one
alkenes: less reactive & isomerization;  357 bottom
Carey B-Chap 4-5ed
Chapter 4