All-Up Reactive Conformation of Chiral Rhodium(II) Carboxylate Catalysts

by
Vincent N. G. Lindsay, Wei Lin, and Andre´ B. Charette*
doi: 10.1021/ja9044955

Chiral Rh(II)-carboxylate catalysts have found widespread use in the field of metal carbene transformations, including asymmetric cyclopropanation reactions.1 Though several enantioselective transformations have been developed to date, little evidence is known
on how the chirality is projected near the reaction center by the chiral carboxylates. Davies et al. have suggested that four main possible symmetries have to be considered, from which only two
possess equivalent catalyst faces (Figure 1, C2 and D2).2 It has been postulated that catalysts having two different carbene-formation sites should not be effective in inducing enantioselectivity, since the more kinetically active and accessible face is apparently achiral (C1 andC4).

However, Fox et al. recently contradicted this concept by reporting the highly efficient asymmetric cyclopropanation of alkenes with R-alkyl-R-diazoesters using such a catalyst, where DFT calculations demonstrated that the all-up conformation of the catalyst plays a prominent role in these reactions.

All our experiments suggest that the halogenated rhodium carboxylate catalysts used in this process react through an all-up conformation, which is consistent with Fox’s DFT calculations made on non-halogenated analogues.

Peptide–Dirhodium Ligation

Controlling Peptide Structure with Coordination Chemistry: Robust and
Reversible Peptide–Dirhodium Ligation
DOI: 10.1002/chem.200901266
Chem. Eur. J. 2009, 00, 0 – 0

interesting paper.

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.
Rh2(ESP)2
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.

ester:
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->