deprotection of dimethyl acetal

1. in a particular substrate bearing a terminal double bond at 5,6 position related to the acetal,
the following deprotection methods failed

Methods tried:                                 results:

1. TFA/water/chloroform                   unknown product, aldehyde/alkene disappeared

2. I2/acetone                                     unknown product, aldehyde/alkene disappeared

3.HCOOH, pentane                          unknown product, aldehyde/alkene disappeared

4. TESOTf, 2,6-lutidine                       no reaction

the following method is successful:

DDQ/MeCN/water rt.

How to prevent N-Cbz from falling off in hydrogenation condition ?

N-Cbz is sensitive to H2/pd/c even in basic condition (TEA).
Known methods to prevent N-Cbz from falling off when doing hydrogenation reactions are not many.

1. Pd/c (en), H2, THF by Kosaku Hirota
pd/c (en) is pd/c deactivated by ethylenediamine. It is developed for chemoselective hydrogenation of reducible functionalities such as olefin, acetylene, nitro, azide, aromatic bromine or benzyl ester moieties, in the presence of O-Bn or N-Z protective
groups.
alkyl N-cbz is stable while double bonds are saturated.
aryl-N-cbz is unstable under this catalyst.
H. Sajiki, K. Hattori and K. Hirota, J. Org. Chem., 1998, 63, 7990.

2. Pd(OAc)2, DPPF,TEA, dmf,formic acid
Can do deoxygenation of phenol by OTf in the presences of N-Zbz.

3. squaric acid derivative/pd/c/H2
works ok, can saturate double bond without touch n-cbz.

4. pd/c/ph2s/H2
also can saturate double bond without touching n-cbz.

5. Pd(OAc)2, DPPF, TEA, dmf,formic acid, Et3SiH
works for deoxygenation of phenol triflate in the presense of N-Cbz.

Note:
1. pd/c(en) was tried. but n-cbz falled off quickly.
2. dppe/pd/formic acid method is OK.
3. ph2s/pd/c/h2 didn't touch N-cbz in my hand. but can't do deoxygenation of a phenol.

deprotection/protection of allylether

1. formation of allyl ether.
allylbromide/base

2. deprotection.
1. pdcl2/acoh/Naoac/water. heated to 70C for 2 hr.
works ok, but sometimes cause decomposition of my sugar compound.
2. pd(PPh3)4/acoh, 80C. 2hr.
works great, high yield. rxn started even before heating at rt!

An example of protection of alkene by Diels-alder rxn

New approaches for the synthesis of erythrinan alkaloids

Org. Biomol. Chem., 2009, 7, 1963–1979

retro d-a reaction happened by heating in vacuum. 80% yield.

benzylidene acetal of glucopyranoside

formation:
1. bnezaldehyde -ZnCl2
2. benzaldehyde dimethyl acetal 3 eq.- TsOH 0.1 eq. in MeCN, refluxing. 2hr.
works great. >60% yield.
workup procedure:
remove mecn to about half invacuo, then NaHCO3 aq. solution added to quench TsOH. Further remove meCN completely invacuo.
EtOAc used to dissolve the product. wash with naHCO3,brine. then concentrated.
Add acetone to dissolve the solid. Add hexanes to precipitate the product. product collected by filtration.
(EtOAc is not a good solvent for the product, so have to use acetone, benzaldehyde dimethyl acetal can dissolve in hexanes).

the rxn is reversible, so base should be used to destroy the catalyst after done.

3. phCHBr2 -base

4. benzaldehyde dimethylacetal , I2 in MeCN ,rt. 1-2 hr.
although the author claimed more than 90% yield, I can only get about 30-40% yield after workup( Na2S2O3 quenching). the author also claimed a simple workup by vacuum away MeCN and I2, but removal of I2 by vacuum is really not practical.


removal:
1. MeOH, I2, reflux, 2 hr
works great, >80%
2. MeOH, TsOH, rt

deprotection of benzyl on an amine

1. pd/c, hydrogenation.
known to be slow compare to benzyl ether.
acidic solvents like HCl/MeOH or AcOH was reported to give good results.

2. CAN/MeCN/water
mild condition, but works only for tertiary amine.

3. substitute the benzyl group with a carbamate, then remove the carbamate by various ways.
ex. vinyl formate ,allyl formate, trichloro ethyl formate,

4. oxidize it to benzoyl, then hydrolysis.

deprotection of benzyl methyl ether.

1. BBr3.
popular.
2. BCl3, works for meta-carbonyl benzyl methyl ether.

3. alcl3,dcm
other ether can also be removed.

4. Et3SiH/(C6F5)3B then TBAF
very gentle condition.

5.HBr 48% solution, tributylhexdecylphosphonium bromide.
6. HBr, AcOH
7. PBr3.
conclusion: halide is essential. an oxygen-philic element is also important( usually an element with empty atomic orbitals).

7. LiCl/DMF/ heat
tolerates 1,2-diketone.

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.