Isomerization of conjugated double bond

Recently found an interesting reaction which isomerized the conjugated double bond by the following sequence:
1. ketalize the ketone by acid/ethylene glycol. during which rxn the double bond isomerized to the more substituted position.
2. remove the ketal by oxalic acid which is efficient and mild enough to keep the double bond from isomerization to the more stable conjugated position.

very cool transformations, which demonstrated the author's deep understanding of those reagents and the beauty of organic transformations.
the paper was published about 30-40 years ago in jacs.

Hydrogenation of double bond

1. heterogeneous metal catalyst.

1. pd/c is better than pt. because it won't hydrogenate aromatic rings.
2. Benzyl ether and trityl ether can be kept by addition of nitrogen containing base (Py, TEA, ...), the selectivity is very good.
3. Benzyl ether reduced quicker in THF than in MeOH.
3. Ir black gives better facial selectivity than Pd/c, PtO2.
4. hydrogenation in polar solvents is quicker. AcOH>MeOH>EtOH>THF. But facial selectivity is worse.
5. trace of water can activate the metal surface. Good for both hydrogenation and benzyl removal.

2. homogeneous catalysts
wilkinson's catalyst, facial selectivity is bad.

3. hydrazine reduction.
active NH=NH generated by heating tosylhydrazine with base.
very useful when a gental touch is desired.
can reduce triple bond to double bond.

alkene to alkyne

1. dibromination.
DCM. 0 C or -78C if you have bromine sensitive group( for example: benzyl ether)

2. 2 eq. Base.
strong base is needed.
LDA or KHMDS.
n-BuLi is not good.


note: if you have a heteroatom ( oxygen ) alpha to you dibromide, you can use weaker base to make it into alkyne (DBU)

petasis reagent: (cp)2Ti(cyclopropane)2

Cp2Ti(cyclopropane)2 is used to convert a ketone into cyclopropane-alkene.

1. making of this reagent.
Li,Et2O, 0 C, add cyclopropanebromide dropwise into the solution.( very exothermic).
low sodium Li can be used. 1hr at rt, then the solution was transfered into a Et2O solution of Cp2TiCl2 at 0 C. stirred for 90 min, quenched by ice water. washed, dried over MgSO4, concentrated. red solid. dissolved in toluene (0.5-0.8 mol/l). The solubility is poor in toluene, so can't make more concentrated). stored in freezer. Solid will be precipitated from the solution in the freezer, so warm it up before use.

2. reaction.
usually, 3-5 eq. of the reagent, toluene as solvent, 50-55C. overnight.
the product is very easy to isomerize to other alkene-isomers. So during the reaction, some NaHCO3 solid can bee added to prevent isomerization.

Stereoselective Olefin Isomerization Leading to Asymmetric Quaternary Carbon Construction

a good article by Prof. Scott Nelson, University of Pittsburgh, Org. Lett., 9 (12), 2325 -2328, 2007.

1. The olefin isomerization-Claisen rearrangement (ICR) sequence allow the transformation of an oxygen chirality into carbon chiralities.

2. this method allows adjacent quaternary-tertiary stereocenter relationships to be established with excellent diastereoselection.

3. Notice in the Figure 2, the only difference of the products are the quartary centers.

Dehydration of alcohol

1. MsCl, then strong base.

2. SOCl2/Py

3. POCl3/Py
some examples indicate that a primary alcohol can be kept intact when dehydrate a tertiary alcohol.

Convertion of alkene to ketones

1. hydroboration
alcohol on the less hindered carbon.

2.Wacker oxidation.
very gentle condition. internal alkene is still problematic.

3.alkene to epoxide, then hydride opening of the epoxide gives alcohol on the more substituted carbon. If use Cp2TiCl mediated radical reduction,then gives alcohol on the less hindered carbon.

4. Hg(OAc)2/H2O.
a very gentle condition. gives hydromercury, then NaBH4 radical reduction gives the alcohol on the more substituted carbon.

5. make bromohydrin first, then pd will eliminate the bromide and gives the ketone on the more electronphilic carbon.

criegee rearrangement

1. O3 to get the ozonide, then remove solvent, Ac2O/...?/reflux
= ozonolysis/pph3 + Baeyer-Villiger rearangement.
nice reaction.

Hg(OAc)2 mediated hydrolysis of alkene

1. Hg(OAc)2/THF/H2O then NaBH4/NaOH/H2O
Hg++ acts like Br+,
NaBH4 reduces Hg to H.
gives different alcohol compared to Borane.

Wacker oxidation

1. PdCl2/CuCl/DMF/H2O/O2/temp
usually only for terminal alkene, methylketone is the product.

2. internal alkene is less reactive and no regioselectivity.
If the internal alkene has an allylic alcohol, product will be only bata-alcohol ketone.

3. catalytic amount of Cu(OAc)2 can be used.
this condition is less reactive, but some acid sensitive groups can be preserved, and also yield can be higher.

selectivity of epoxidation by mcpba

electron rich alkene reacts first,
tri-sub alkene reacts first, then di-sub alkene.
NaHCO3 can be added to neutralize the acid generated.

convert ketone to alkene

wittig
basic reagent, may cause problem if ketone is enolizable.


tebbe, petasis regaent
non basic, works for enolizable and steric hindered ketones.

cleavage of double bond to diol

OsO4/NMO/acetone/water
K2OsO4 can be used instead of OsO4, purple powder, easy to handle.
OsO4 dissolves in CCl4. very toxic.
don't use excess NMO. In my case, some unknown compound isolated if large excess NMO used. Since OsO4/oxone can cut double bond just as ozonolysis, not a surprise.

Hydrocarboxylation of alkene

several conditions available.
1. Pd /ligand /CO/MeOH/TsOH or MsOH
elevated temp, CO >1 atm,
if you have a isopropyl group on the terminal, then ester adds to the 2-carbon!
2. Ru2(CO)12

internal alkene can be isomerized and forms terminal carboxylate.

Hydroboration of alkenes

BH3, thexylborane, Sia2BH ,9-BBN

Boron atom adds to the less hindered carbon. Sia2BH gives aldehyde(alkyne addition).
after quenching by base, oxidation removes the boron and gives an alcohol.

H2O2, sodium borate can be used to oxidize the borane.

dimethyl sulfide/1,4-dioxane can stabilize BH3 in THF.

Borane can easily chelate with oxygen atom(ex. protected alcohol). In some case, may give unexpected product.

BH3 took off TBS in my case.

xanthate chemistry

1.formation
1. DBU in DMSO, CS2, MeI.
this condition can't isomerize an ester.
2. NaH/THF.

2.thermal elimination
heated to 180C, syn elimination happened, double bond formed.
3. reductive elimination.
with Bu3SnH.aibn. radical rxn.
can be done at rt with water, described by John Wood.

asymmetric epoxidation

Sharpless epoxidation
allylic alcohol only.
homoallylic alcohol can also be reactive using some more active metal.

Jacobsen epoxidation

not limited to allylic alcohol, tetra-sub alkene gives low ee.

Shi epoxidation


Sulfur Ylide Epoxidation

cordova's epoxidation
works for electron deficient olefins.

taber's mandelic acid approachbased on column separation of two mandelic ester diasteromers.
Works on Terminal alkenes.