Organocerium reagent

Organocerium Reagents. Reduction in Grignard reactions of hindered ketones can severely limit a carbonyl alkylation reaction. This limitation can be circumvented, however, by the converting the Grignard 

Chapter 8. Nucleophilic Species That Form Carbon-Carbon Bonds 

Organolithium reagents (sec. 8.5) are also useful precursors. Vinylcerium reagent 180 was prepared from vinyl bromide 179 in Ovaska s synthesis of fused polycyclic ring systems.When this reacted with 181, alcohol 182 was isolated in 61% yield after hydrolysis. 

More reactive substrate Less reactive substrate Selectivity (%) A B C B (unreacted) 

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The corresponding organocerium reagent derived from R2MgX failed. 

Organocerium reagents have been found to improve yields in additions to bicyclo[3.3.1]nonan-3-ones.200... 

Amides, especially of piperidine and morpholine, give good yields of ketones on reaction with organocerium reagents.203 It has been suggested that the morpholine oxygen may interact with the oxyphilic cerium to stabilize the addition intermediate. 

Organocerium reagents also show excellent reactivity toward nitriles and imines,205 and organocerium compounds were found to be the preferred organometallic reagent for addition to hydrazones in an enantioselective synthesis of amines.206... 

List several features of organocerium reagents that make them applicable to specific synthetic transformations. Give a specific example illustrating each feature. 

The same authors also reported the stereoselective addition of organocerium reagents to 1,3-ketoalcohol 11 involving titanium alkoxide intermediates (Scheme 4).8... 

A similar but bulkier organocerium reagent 26 was applied to the total synthesis of bilosespenes A and B.1S Upon reaction of 26 and ketone 25, the target intermediate 27 was obtained in 76% yield as a single isomer (Scheme 9). 

Barbier-type organocerium reagents reacted with Af,Af-bis[(A)-l-phenylethyl]ethanediimine 31 to form 1,2-aminoal-cohol 32 via hydrolysis of the initially formed iminoamine product by water released from CeCl3 hydrate (Scheme 10).17 Aminoalcohol 32 was produced as a sole product. 

Several reviews and research papers discussing the application and extension of this method have appeared.40 For example, Weber et al.41 reported an interesting result in which cerium acted as a counterion in the modified proline auxiliary (SAMEMP 40) for selective addition of organocerium reagents to hydrazones. The initial adduct was trapped with either methyl or benzyl chloro-formate to afford the stable /V-aminocarbonatc 41 (Scheme 2-24). From this example readers can see that this proline chiral auxiliary can be used not only for a-alkylation but also for nucleophilic addition, which is discussed in detail later. 

In the study of Weber et al.,41 a series of proline-derived hydrazones were prepared, and the reactions of the hydrazones with organocerium reagents were examined. It is clear from the table in Scheme 2 24 that the diastereoselectivity of the examined reactions depends on the nature of the side chain. (S )-l-amino-2-(2-methoxyethoxymethyl) pyrrolidine (40) gave the highest selectivity for various nucleophiles. 

An organocerium reagent gave better yields than either the lithium or Grignard reagents in addition to carbonyl at the 17-position on steroids.156... 

Alkynylvanadium(III) chloride, 219 Chromium(II) chloride, 84 Lithium methoxyacetylide, 166 Organocerium reagents, 206 Titanium(IV) chloride, 304 Propargyl groups... 

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