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tence of the proposed pyran intermediate V and 6p-electrocyclic
ring opening in the last step was supported by the last control
experiment [ESI† 1.4. eqn (iii)]. When the reaction time for the
synthesis of (E)-12 was increased to 24 h, a dihydro pyridinone
derivative 24 (22%), along with the desired compound (E)-12
(34%), was formed, indicating that the in situ generated reactive
allene was trapped by secondary amide,20 followed by double bond
isomerization to generate compound 24. However, the mixture
((E/Z)-6a and 6a0) could be generated by the competitive [1,3]-H
shift21 of an acidic a-proton from the allenoyl fluoride II leading to
amidation or esterification (Scheme 4, highlighted with grey
colour). The preferred pathway depends on the substituent at
the a, b or d-position,22 and isomerization may also have been
instigated by an impurity in the reaction medium.17a
In summary, we have developed a new synthetic protocol for
the direct stereoselective synthesis of functionalized a-substituted
2,4-dienamide via three-component reactions of gem-difluorochloro
ethanes, propargyl alcohols, and amines. The versatility of this
method for various substrates can be utilized for the efficient
stereoselective synthesis of a-substituted 2,4-dienamide containing
molecules.
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This work was supported by the National Research Foundation
(NRF-2017R1A2A2A05001433, NRF-2018M2A2B3A02071842, and
NRF2018R1A4A1024713) and the Korean Health Industry Devel-
opment Institute (HI16C0947).
Conflicts of interest
The authors declare no conflict of interest.
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14358 | Chem. Commun., 2019, 55, 14355--14358
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