Sunday, October 28, 2007

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.

Sunday, October 14, 2007

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.

Monday, October 8, 2007

protection of ketone by Li enolate.

convert ketone into Li enolate by LDA in THF at -70 C.
the enolate formed is very stable below -30C, LAH can't reduct it.
LAH can't reduce ester below -40C at THF. So warm up to -40- -30C, the ester will be reduced while the ketone remained.
In one run, the Li enolate is stable even at about 0 C!

Reduction of ketone

1. Meerwein-Ponndorf-Verley Reduction
thermodynamic alcohol is formed instead of kinetic product (compare to LAH).
Al(OR)3 ,i-prOH.
lanthanides are m
ore reactive, for example Gd.

2. LAH
solvent THF or Et2O. Exothermic, slow addition!
when quenching LAH reaction, if x gram LAH used, then add x g water, x ml of 15% NaOH in water, 3x gram of water finally. Then a easy filtering through a celite pad will remove all the metal.

3. NaBH4
reduces ketone, not ester.
solvent: MeOH/THF.

4. DIBAL-H
reduces ester to aldehyde.

cationic cyclization

initiator:
alcohol,alkene,
epoxide, ketone, ketal,
acid, acid chloride,
C=N+ -> N-C+
R-SO2Ph, R-NO2,

terminator:
alcohol,
azide, ketone, ketal, ester, beta-ketoester.
Enone, TMS enone ether, allyl silane
acytylene
alkene, C=NR,
aromatic, indole

a very good pdf about cationic cyclization:
http://cmds.kaist.ac.kr/skim/lecture/1.Cationic.pdf

Saturday, October 6, 2007

making of beta-ketoester

adds methylester to a methyl ketone to form beta-ketoester:
1. NaH/toluene/dimethylcarbonate/reflux, trace of MeOH to initiate the reaction,
then add the methylketone dropwise into the reaction mixture.
reaction is very exothermic, add slowly.
KH or DMF can also be used to initiate the reaction.
kinetic enolate is formed.

2. LDA/HMPA, cyano methylcarbonate (mander's reagent). -78C.
C-alkylation. if chloro methylcarbonate was used, only O-alkylation product.

HMPA

polar aprotic solvent.

1. can chelate with Li, improves basicity of LDA.
also increase the stability of LDA. ( without hmpa, LDA in THF became gray above 0C. with HMPA, LDA in THF can go beyond 0C.)

2. can chelate with Cu for 1,4 addition.

very useful.

organomagnesium

less basic than organolithium?

usually stable in THF at rt. Can be made in reflux THF or ether.

1,2 addition. (for enolizable/stericly hindered ketones, use CeCl3)

To initiate the reaction between halides and Mg,
1. heat,
2. I2 can be used.
3. broken glass can also be used.
4. distill organohalides with CaH2 can also help.

Reaction is very exothermic.
usually, Grignard made from RBr is more reacitive than RCl.

organolithium reagent

1. vinyl lithium can't be made directly. tetravinyltin was used to make vinyllithium.
2. RLi is not stable in THF at rt, so Et2O was used as the solvent. control temp at 0C or lower.
3. High sodium Li metal is more active than low sodium Li.
4. Argon should be used instead of N2 when store Li wire in bottle, since Li can react with N2.
5. Excess Li can be used and CuCN can be added directly into the reaction mixture containing Li at -40C. The Cu+ won't be reduced by Li metal.
6. broken glass can be added with Li to improve reactivity. it works as a Li surface scratcher.
7. alky lithium is very basic, stable temp is lower than vinyl lithium.

Cu mediated 1,4 and 1,5 addition

1. 1,5 addition means opening of cyclopropane conjugated with a beta-ketoester.
organocupper made by organolithium works better than organocupper made by organomagnesium halide. The reason is believed that the Li can chelate with oxygen.
Cu2R made by MgR gives only 1,2 addition while Cu2R made by RLi only gives 1,5 addition.
R is 1-bromo-2-methylpropene. reaction condition: R, Li,broken glass,Et2O, 0C, then -40C, THF,HMPA,CuCN, substrate.
half eq. of CuCN is used to make the active Cu2R.

1. dummy ligand can be used to save half the bromide.

Wednesday, October 3, 2007

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.