Rearrangement reactions chiral lithium amides

Phosphate-derived a-oxycarbanions can rearrange into a-hydroxy phosphonates. This class of rearrangement is known to proceed with retention of configuration at the carban-ion terminus. The enantioselective version of this rearrangement has been developed using a chiral lithium amide as a base (equation 115) . The reaction of benzyl dimethyl phosphate 182 with amide R,R)-63 in THF gave the hydroxy phosphonate (5 )-183 in 30% in enantioenriched form (52% ee). 

More recently, they have reported an enantioselective reaction via an a-sulfi-nyl carbanion involving rearrangement to a vinyl sulfoxide [Eq. (16)] [61]. Treatment of an episulfoxide with a chiral lithium amide followed by methyla-tion yielded a methysulfinylcyclopentene with high enantioselectivity. In this reaction, the enantioselection occurs in the first deprotonation step. 

Other Enantioselective Reactions. Enantioselective epoxide elimination by chiral bases has been demonstrated. More recently, the enantioselective [2,3]-Wittig rearrangement of a 13-membered propargylic ally lie ether has been performed using the lithium amide of (f ,f )-(l) as the base for deprotonation (eq 15). For this particular substrate, THF is a better solvent than ether, although pentane produces better results in a related transformation (eq 16). In fact, a change in solvent in this type of reaction has been shown to lead to a reversal of the stereoselectivity of the transformation. ... 

Imidate esters can also be generated by reaction of imidoyl chlorides and allylic alcohols. The lithium anions of these imidates, prepared using lithium diethylamide, rearrange at around 0°C. When a chiral amine is used, this reaction can give rise to enantioselective formation of 7, 8-unsaturated amides. Good results were obtained with a chiral binaphthylamine.265 The methoxy substituent is believed to play a role as a Li+ ligand in the reactive enolate. 

The pioneering work on enantioselective [2,3]-Wittig rearrangement was carried out by Marshall and Lebreton in the ring-contracting rearrangement of a 13-membered cyclic ether using lithium bis(l-phenylethyl) amide (63) as a chiral base (equation 34). Upon treatment with a (S,S)-63 (3 equivalents) in THF at —70 to —15 °C, ether 64 afforded the enantioenriched [2,3]-product 65 in 82% yield with 69% ee. The reaction was applied in the synthesis of (+)-aristolactone (66). 

In an attempt to achieve an enantioselective Eschenmoser-Claisen rearrangement with amide salts 6, (2R,5R)-l-(fluoroacetyl)-2,5-dimethylpyrrolidine was methylated to give chiral 6d. 5 Reaction of 6d with the lithium salt of (fj-crotyl alcohol gives amide 7d as a mixture of diastereomers, in which the. vj rt-isomers predominate. 

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