3-lithio-5-bromo-2-methoxy

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

The bromine group in 4-bromo-5-methoxy-2-trifluoromethyl-l,10-phenanthroline has been replaced by lithium with w-butyllithium and the lithio derivative reacted with pyridine 2-aldehyde.215... 

In the total synthesis of nalanthalide, the crucial coupling of the 7-pyrone moiety with the diterpenoid core was achieved by lithium halogen exchange of 3-bromo-2-methoxy-5,6-dimethyl-4/7-pyran-4-one 353 and addition of the resulting 3-lithio-7-pyrone 354 to aldehyde 355 to produce 356 in an impressive 87% yield (Scheme 53) <2005OL3745, 2006TL3251>. 

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