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. 2012 Nov 2;14(21):5400-3.
doi: 10.1021/ol3024117. Epub 2012 Oct 12.

Chichibabin-type direct alkylation of pyridyl alcohols with alkyl lithium reagents

Jenna L Jeffrey  1 , Richmond Sarpong
Affiliations

Chichibabin-type direct alkylation of pyridyl alcohols with alkyl lithium reagents

Jenna L Jeffrey et al. Org Lett. .

Abstract

Direct C(6) alkylation of pyridyl alcohols can be achieved following an initial deprotonation of the hydroxy group. This transformation, which is believed to occur by a Chichibabin-type alkylation, avoids lateral deprotonation prior to pyridine ring alkylation and gives increased regioselectivity for C(6) over C(4) alkylation.

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Figures

Figure 1
Figure 1
Challenges with direct C(6) functionalization of picoline derivatives by alkyl nucleophile addition
Figure 2
Figure 2
Examples of pyridyl alcohol utility
Figure 3
Figure 3
Products of the direct alkylation of selected pyridyl alcohols. as-BuLi was used as the base; bt-BuLi was used as the base; cMeLi was used as the base; dPhLi was used as the base.
Scheme 1
Scheme 1
Proposed facilitation of Chichibabin-type alkylation of pyridyl alcohols (2)
See this image and copyright information in PMC

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