Jeffery’s conditions

Unfortunately, this process gave good results only with bulky substituents at the acetylenic terminus in 104 and, surprisingly, Jeffery s conditions—but without a quaternary ammonium salt—were found to work best. With an additional alkenyl substituent at the acetylenic terminus as in the cyclohexenyl-substituted 2-bromonona-l,8-dien-6-yne 109, the co-cyclization with bicyclopropylidene 12, under these conditions, leads to 110. This transformation involves two consecutive 67r-electrocyclizations of the initially formed cross-conjugated pentaene 111, which was not isolated (Scheme 30). ... 

In addition, the application of Jeffery s conditions by Sinou and co-workers, with extra triphenylphosphine and tetrabutylammonium hydrogensulfate, confirmed that Cul is not essential to success in alkyne coupling reactions [24], Moreover, they reported the most efficient coupling of bromoanisole with propargyl alcohol in 81% yield. These results prompted the authors to apply these conditions in a cascade reaction, consisting of an intermolecular Heck reaction followed by cyclization of the intermediate cr-complex (Eq. 9). The product, which is a mixture of (E) and (Z) stereomers (approximately 1 1), was sometimes contaminated with a by-product resulting from aromatization, especially for longer reaction times. 

Later, Reetz and coworkers pointed out the role of Pd colloids in phosphine-free Pd-catalysed Heck reactions, as typically encountered under Jeffery s conditions (Pd(OAc)2, Bu4NBr, K2CO3). Studying the Heck reaction of iodobenzene with ethyl... 

COgCHa K2CO3, BU4NCI, CHaCN, 50 C Scheme 10.4 Heck reaction on aryl iodides using Jeffery s conditions. 

In addition, the application of "Jeffery s conditions by Sinou and co-workers, with extra triphenylphosphine and tetrabutylammonium hydrogen sulfate, confirmed that Cul is not essential to success in alkyne coupling reactions [24]. Moreover, they reported the most efficient coupling of bromoanisole with propargyl alcohol in 81% yield. 

Jeffery s conditions are so mild that reaction of an alkenyl iodide containing a very unstable peroxide group 49 proceeded smoothly without decomposition of the peroxide under the conditions at room temperature [37]. 

Many successful apphcadons of Jeffery s conditions have been reported. However, Rawal reported in his alkaloid synthesis that Jeffery s conditions were not suitable for the attempted cyclization of the iodide corresponding to 52 (Br I), and the cyclization of the vinyl bromide 52 proceeded cleanly under a nonpolar set of conditions Pd(OAc)2, PPhs, proton sponge in toluene at 100 °C to give 53 in 82% yield [39],... 

A remarkable effect on rate enhancement under high pressure is known [40]. The enantiomerically pure isoquinoline 55 was obtained from the bromide 54 in 70% yield and with high diastereoselectivity (16 1) under pressure (10 kbar). The yield was lower than 10% under normal pressure and even under Jeffery s conditions [41],... 

Yields of endo cyclization products of the iodo enamine 199 to give the heterocycles 200 steadily increase with longer chain lengths under Jeffery s conditions. It is surprising that the medium-sized (eight- and nine-membered) rings were obtained in high yields [94]. 

An interesting example which shows different catalysts are required for HR of a vinyl bromide and an aryl bromide was observed in enantiopure synthesis of estrone by double HR [100], The vinyl bromide in 217 preferentially reacted with 218 to give 219 selectively in 61 % yield without giving a double bond isomer using Pd(OAc)2 and PPhs. Then 219 was converted to 220 in 99% yield under Jeffery s conditions using the Herrmaim complex (XVIII-1) as a catalyst. On the other hand, the one-pot domino reaction of 217 with 218 under the same conditions afforded 220 in 35 % yield. 

Total syntheses of the complex molecule of strychnine have been carried out by several groups applying intramolecular HR as key reactions. The first elegant Pd-based total synthesis of stryclmine (237) has been achieved by Rawal. An intramolecular Diels-Alder reaction and HR were key reactions. The Pd-catalyzed cyclization of the pentacyclic lactam 238 under Jeffery s conditions gave isostrychnine 239 in 74% yield. Conversion of 239 to 237 is known [106]. 

Two Pd-catalyzed cyclizations were used for the enantioselective synthesis of (—)-cephalotoxine [109]. One-pot Pd-catalyzed domino reactions, namely intramolecular allylation of amine and HR of 256, seem to be the best path for the desired synthesis. However, attempted direct conversion of 256 to 258 with the Herrmaim complex was unsuccessful. Then selective intramolecular aminoallylation with the chiral cyclopentyl acetate occurred smoothly to give the Spiro amine 257 in 88 % yield when Pd(PPh3)4 and TMG (tetramethylguanidine) as a base were used. The cyclization proceeded with retention of stereochemistry without racemization. The next HR reaction of 257 gave the seven-membered compound 258 in 81% yield under Jeffery s conditions using the Herrmann complex as a catalyst. No transformation of 257 to 258 occurred when Pd(PPh3)4 was used. The results show that the best catalysts for the allylation and HR are different. 

Orr/zc- em-Dihalovinylanilines 278 were also used in another example of a Buchwald-Hartwig-type/Mizoroki-Heck reaction for the synthesis of 2-vinylic indoles 279 (Scheme 8.69). Lautens and coworkers [140] recently illustrated a domino coupUng under Jeffery s condition where the aniline nitrogen undergoes an amination step followed by a Mizoroki-Heck coupling with various alkenes. In this process, electronic factors and steric hindrance of the different substituents had only a small effect on the yield however, in the formation of 3-substituted indoles using this method only very poor yields were obtained. The procedure can also be performed in an intramolecular mode leading to tricycUc compounds such as pyridino and azepino indoles 281 and 282 (Scheme 8.69). 

The Heck reaction has also proved extremely useful in the synthesis of highly conjugated organic materials. For example, using Jeffery s conditions, extended derivatives of paracyclophane 79 were prepared. ... 

Regardless of the active species, importantly, Jeffery s conditions allowed the reaction to be carried out at < 100 °C, at least in the case of aryl... 

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