Table 4. Complete synthesis of difluoro-VCP precursors 19–27 ^a .

Entry ( b )	R1	R2	R3	VCP	Yield c (%)
					E-Alkene (a)	Z-Alkene (b)
1 (A)	Ph	CON(OMe)Me	H	19	74	9
2 (A)	Ph	CO2Et	Me	20	74	0
3 (B)	Ph	H/CN	H/CN	21	84 d
4 (A)	2-Piperonyl	CO2Et	H	22	50	n.d. e
5 (A)	2-Furyl	CO2Et	H	23	Full conversion f
6 (A)	2-Thiophenyl	CO2Et	H	24	Full conversion f
7 (A)	2-Furyl	CO2Et	Me	25	Full conversion f
8 (A)	2-Thiophenyl	CO2Et	Me	26	Full conversion f
9 (A)	3-Me-2-furyl	CO2Et	H	27	Full conversion f

^a Compounds represented by numbers and suffix a and b correspond to E- and Z-isomers, respectively.

^b Synthetic methodology based on Scheme 5.

^c Isolated yields unless otherwise stated.

^d 21a and 21b could not be separated by column chromatography and instead were isolated as a 3 : 2 mixture, respectively (mixture determined by ¹H NMR).

^e 22b formed during the reaction but could not be separated from a mixture with 22a (21% isolated yield of 22a/22b mixture).

^f All precursors were successfully formed but reactions resulted in complex mixtures due to competing low temperature rearrangements.