Direct preparation of copper organometallics bearing an aldehyde function

• Chem. Commun., 2006, 2486-2488
• DOI: 10.1039/b604259g

Polyfunctionalized organometallics are versatile intermediates in modern organic chemistry, since they allow the formation of multifunctional products.¹ One of the best preparation methods of these organometallic reagents is the halogen–metal exchange reaction.^1e,2 The halogen–magnesium³ and halogen–copper⁴ exchanges have recently been extensively investigated. They allow the convenient preparation of polyfunctional aryl, heteroaryl and alkenyl organometallic reagents that bear various functional groups. The formyl group is present in numerous compounds, but has been regarded as being incompatible with most organometallic reagents.⁵ Only scarce examples of formyl-substituted aryl organometallic compounds have been reported.⁶ In most cases, tedious protection and deprotection steps or an additional oxidation step are required to introduce this sensitive function in a target molecule.

Iodine–copper exchange reaction allows the direct preparation of various new aryl, heteroaryl and alkenyl cuprates bearing an aldehyde group, thus expanding the applications of functionalized copper organometallic species in organic synthesis.

Making of Cu(acac)2, Ni(acac)2.

2 eq. of acetylacetone + 2eq. of NaOMe in MeOH
then CuCl2 2H2O 1eq. in MeOH added slowly at rt.
color changed immediately from green to blue when you add CuCl2 into the solution.
1hr, then concentrated. DCM added to dissolve cu(acac)2. fitered. then concentrated.
Can be recrystallized in MeOH/DCM.

the blue solid can dissolve in DCM, chloroform. can't dissolve in water, very limited solubility in MeOH.
H-NMR is a crab. you can't see any sharp peaks. only a broad peak at about 1 ppm.
IR can be used to characterized it.
Ni(acac)2 can be made similarly.

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->