work up of a reaction

1. usually, in small scale, dilute the rxn mixture with ether and let the rxn mixture pass through a pad of silica gel will remove all the polar/inorganic compounds. then remove the ether by rotavapor and then ready for a column.
2. MgSO4 is better than Na2SO4 as the drying reagent. Much quicker, more efficient and less water.
3. silica gel can also trap water so it is not necessary to use MgSO4 before a column.

Column technologies

silica gel size: 5-20 mesh.
1. dry pack the column. use compressed air to tighten the silica gel.
2. add P.E. from the top. push it into silica gel by compressed air. leave some p.e. on the top.
3. mix the organic compound with a little organic solvent(the solvent should dissolve your compound but not carry it through the column. ex. toluene, dichloromethane) and add the mix to the top of the column.
4. push the mix into the column. then add sand to the column.
5. P.E. as the unpolar solvent, (hexanes is better, because it has a higher boiling point than p.e., so it is less likely to make a hot circle in your column), MTBE as the polar solvent.
6.if 40% MTBE in PE is not polar enough, DCM can be added into the solvent to improve the polarity. if more polar solvent is needed, acetone can be added.
7.better separation can be achieved by using different solvent combinations.
usually, polar solvents are: ethylacetate, MTBE, diethylether,acetone, acetonitrile
unpolar solvents: p.e., hexanes, DCM

an easy separation of some beta-ketoesters

beta ketoesters are quite acidic.
In some cases, shake the betaketoester with NaOH or KOH aqueous solution will make the Na or K salt of the betaketoester.
Depends on the structure of the ketoester, the salts may be soluable in water(K salt are more likely to be water-soluable than Na salt), so it can be extracted into water and then acidified by HCl to give the ketoester.
Na salt has less solubility in both water and organic solvent(ex. ether),so it will form a nice precipitation. an easy filtration can give you 99% Na salt of betaketoester, the drawback is the low yield of the precipitation.

hydrogenation opening of cyclopropane

cyclopropane is less reactive than double bond. It is possible to saturate double bond without touching cyclopropane.

PtO2/AcOH/H2
this is the general way to open the cyclopropane between the less substituted carbons.

if you run the rxn in basic or neutral solvents like MeOH will give ring opening product with less selectivity.

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.

trityl ether protection group

behaves like Bn ether.very bulky, so better selectivity towards primary alcohol.

forming:
trityl chloride, TEA, DCM

easily falled off when contact with Silica gel.(during column)
pretreat the silica gel with 1% TEA in P.E. can prevent it completely.

can be removed by hydrogenation(pd/c, H2), addition of Py can preserve it.

benzyl ether protection group

forming:

1.NaH, THF/DMF, BnBr.
TBAI can be used, more active BnI is formed.

2. CsOH/M.S./DMF or Cs2CO3/ DMF or DMSO, BnBr
Cs is a good base, works for very unreactive alcohol.

3. TfOH, DCM, hexane, benzyl trichloroacetimidate
acidic conditon, works for base-sensitive substrate. generally, low yield.

4. Ag2O, BnBr, solvent,( in darkness)
good selectivity between primary and secondary alcohols. very mild condition.

5. bis(butyl)tin oxide/CsF/BnBr
works for monoprotection of 1,2-diol.

6. Cu(acac)2/BnCl/reflux
only protect primary alcohols.

7.BnCHN2/HBF4
very mild condition. tolerates many functional groups.

8. benzyl chloride/Bu4NBr/NaOH aquous/

deprotection:
1. 5% Pd/c, in THF the reation is faster than MeOH.
addition of base (TEA, pyridine) can prevent benzylether from hydrogenation conditions.(H2, 1 atm, Pd/C, 5%, MeOH).
Removal of trityl ether is slower than hydrogenation of double bond. So short time (1-2hr) hydrogenation won't touch trityl group, of course, base can also be used to pretect trityl group.
removal of benzylether is 20 times quicker in THF than in MeOH(Pd/C, 1atm H2, rt).

2. O3 can oxidize Bn to Benzylester.
3. RuO2/NaIO4 oxidation can oxidize Bn to Benzyl ester.
4. DDQ.
with or without water.
UV/MeCN. (mild condition, can tolerate double bonds).
5. dissolving metal.
Na/Li in liquid ammonia.

chiral pool

1.Evans Oxazolidinone Auxiliaries
2. menthol, camphor, amino acid derivatives.
3. Myers Pseudoephedrine Auxiliaries

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.