Friday, August 17, 2007

C-H Insertion/cyclopropanation (Rh, Cu...)

1. C-H insertion -> cyclopentane/cyclohexane
the biggest side product is the dimer ( two diazo ketone lost one N2). usually unstable carbenoid gives less dimer, for example carbenoid with two electron withdrawing group or the rhodium dimer have electron-withdrawing ligand( for ex. Rh2(pttl)4).
stablized carbenoid reacts slowly so more dimmer, but better selectivity. for example,
In some situation, cyclohexane is formed instead of cyclopentane, rh2(piv)4 gives best 6/5 ratio.

2. double bond inerstion -> cyclopropane

The yield is usually higher than C-H inserstion. if the double bond is in a ring before the reaction, open the cyclopropane by hydrogenation will give CIS-ring fusion product.

3. O-H/N-H insertion.

Common catalysts:

hashimoto's cat.
rh2(pttl)4 , ptpa,....
very active toward intra. C-H insertion of ketones. higgest ee so far.

Davies' cat.
Rh2(DOSP)4, ...
intermolecular C-H or cyclopropanation.
intramolecular also ok.

Doyle's cat.
Rh2(MEOX)4 , mppim....
good for diazo esters. less reactive for diazoketones.

Taber's cat.
two ligands instead of four. ligand stability increased.
no good results so far.

DuBois's cat.
very electron rich ligand. N-H insertion. derived from taber's cat.

diazo transfer reaction
ketone, beta-ketoester:
base: TEA, DBU
diazotransfer reagent: MsN3, AABSA, PNBSA, TIBSA
solvent: DCM, MeCN, Toluene
for a-aryl ketone, TIBSA/toluene/DBU works better.
for beta-ketoester, TEA/MeCN/MsN3 works OK. 1N NaOH can wash away excess MsN3.

Danheiser's method J. Org. Chem. 1990, 55, 1959.
introduced 2,2,2-trifluoroethyl trifluoroacetate and lithium bis(trimethylsilyl) amide as an efficient acylation method.

Taber's method
The TiCl4-mediated reaction of an ester with benzoyl chloride results in high yields of the R-benzoylated ester. Diazo transfer of the benzoylated ester utilizing p-acetoamidobenzenesulfonyl azide affords the R-diazo ester in good yield

acid->acid chloride then treated with diazomethane. TMSdiazomethane is a good substitution, but not in all cases. I did a reaction where TMSdiazomethane is not successful but diazomethane works.

ketone-> hydrazone->


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