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.

Oxidation of alcohol

several conditions and there limitations:
1. Dess-Martin
very good.
2. Swern oxidaion
gives low yield when you have an alpha-benzyl alcohol.
control temp below -65C is important for success of this rxn.
3. P2O5/DMSO
forms sticky solid in the bottle. P2O5 is very sensitive to water, hard to handle.
slightly low yield compared to swern. but works for alpha-benzyl alcohol.
4. TBAP/NMO/M.S.
good.
5. PCC/H5IO6
very good for some substrate, ex. alpha-benzyl alcohol.
6. Jone's reagent
acidic condition, gives acid.
7. PCC/NaOAc/M.S.(1:1:1)
better work up than PCC along.

ozonolysis

Usually in DCM/MeOH at -78C.
Why MeOH?
literature said MeOH can keep ozone longer in solution. Actually once I did it without MeOH, big scale, The result is that I can't see the blue color! So MeOH can also serve as an indicator!
If you have another functional group which is also sensitive to ozone, you can use an indicator, sudan III is one.
Triphenylphosphine or dimethyl sulfide can be used to workup the ozonide if you want a ketone.
Zinc dust is also OK.
NaBH4 is used to reduce the ozonide to alcohol. Now MeOH is important because it can dissolve NaBH4.

A good alternative way to cut the double bond is to use PhIO in water. J. Am. Chem. Soc., 129 (10), 2772 -2773, 2007.

alkylidene carbene insertion

formation: vinyl halide (-70C, DME, KHMDS).
or ketone + (Li-TMSdiazomethane), aldehyde will give (alkyne?)
the above reactions are very sensitive to steric hinderance. In my experience, ketone with a alpha quartary center can't react.

transformation of Ketone to Nitrile.

1. TOSMIC
ketone sensitive to MeO- will be destroyed during the reaction. for example beta-ketoester.

2. 1. tosylhydrazine/MeOH to form the hydrazone, then 2. KCN, MeOH, heat.
1. triisopropylbenzylsulfonylhydrazones or trimethylbenzylsulfonylhydrazones have quicker decompose rate than tosylhydrzones. To form the hydrazone, acid (eg. sulfuric acid) usually used to catalyze the reaction. Addition of water can also make the hydrazone formation faster.
2. In the second reaction, acid usually used to make HCN in situ from KCN, which is more reactive.
3. works even for very hindered ketone, for example, ketone with two alpha quaternary carbon center.
4. If temp. goes too high, elimination will happen and you will get an alkene if the ketone has a-hydrogen.

3. reduce the ketone to alcohol, make a leaving group (MsO-),
then treated with NaCN/DMF/water. Sn2 rxn.

Baking Yeast Reduction

enantioselective, reduce beta-keto ester to beta-hydroxy ester.

brand : red star active dry baking yeast.

fermented yeast (sucrose or ethanol) reacts really slow and not efficient. and after the reaction, separation procedure is really time costing.

Use P.E. and water as the solvent and non-fermented yeast works better. shorter time and higher yield. work up is greatly improved. Acetone was used to extract the reaction mixture, works great.

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.

CeCl3 assisted Grignard rxn

Organomagnisum compound can react with CeCl3 to form some complex so the basisity is reduced.
both hinded and enoliazable ketones can be reactive under CeCl3.
1,2 addtion in most of the cases.
CeCl3 drying process: 90C 4hr, 140-150C 2hr under high vacuum. (0.1-0.2 Torr)
several conditions available:
1.CeCl3/THF
sonication is better than stirring, 1 hr at rt is good enough.
grignard added into CeCl3 at -78C, then ketone.
2.CeCl3 with TiCl4
Even beta-ketone ester can be alkylated to the the beta-alcohol ester! Only successful when gama position is phenyl.
3.CeCl3.2xLiCl in THF