Heck reaction, tandem

The asymmetric Wacker methodology has also been extended to include a tandem Heck reaction.416 An elegant... 

In these Heck reactions some degree of enantioselectivity (up to 83% ee) is achieved in the presence of (/ )-BINAP, although the yields of Heck products are often very low in the highest degree of enantioselectivity (e.g., 19% isolated yield at 83% ee) [93]. An example of a tandem Heck reaction is shown below involving the arylation of dihydropyrrole 132 with 1-naphthyl triflate (133) [92]. Complete chirality transfer is observed for the arylation of 134 to 135. 

A related tandem Heck reaction is seen in the conversion of 145 to 146, wherein the pyrrole ring is the site of termination [102],... 

Whereas Hegedus [335] and Danishefsky [336] were the first to discover a tandem Heck reaction from o-allyl-A -acryloylanilines leading to tricyclic pyrrolo[l,2-a]indoles or pyridino[l,2-a]indoles [336], it has been the fantastic work of Grigg to unleash the enormous potential of this chemistry. Grigg and his co-workers parlayed their Pd-catalyzed tandem polycyclization-anion capture sequence into a treasure trove of syntheses starting with IV-allyl-o-haloanilines [337-345], Diels-Alder and olefin metathesis reactions can be interwoven into the sequence or can serve as the culmination step, as can a wide variety of nucleophiles. An example of the transformation of 289 to 290 is shown below in which indole is the terminating nucleophile [340],... 

A schematic of the Heck reaction is shown in Scheme 10.1, although it is worth noting that many variations on the Heck reaction, such as intramolecular and tandem Heck reactions, are known. 

The first reaction is unique in a sense that both a five and a six membered heterocycle are formed in a tandem Heck reaction step. Closure of a five membered ring followed by the closure of the six membered ring converts the enamine shown in 5.8. to the isoindoloneisoquinoline framework.8... 

Dihydroxy-l,3-dioxepins readily undergo vinylacetal rearrangement in the presence of a Lewis acid to give tetrahydrofuran-3-carbaldehydes (CHEC-II(1996)). This methodology was applied in a tandem Heck reaction -rearrangement process for the synthesis of a variety of 2,4-substituted tetrahydrofuran-3-carbaldehydes (Scheme 19) <2006CC3119>. 

Scheme 6-24 Tandem Heck reactions from total syntheses of ( )-scopadulcic acids A and B.

Z-tamoxifen 403 tandem cyclization 290, 295 tandem Heck reaction-anion capture 253-4 tandem Heck reaction-phenoxide capture 253 tandem Heck reactions 251, 252-4 tandem intramolecular Heck-intermolecular Stille cross-coupling 255 taxol 140, 143,243,245 ( )-tazettine 146,234 telomerization 352 telomerization products 343, 345 template effect 140 teraconic anhydride 468 terminal acetylenes, synthesis of 216-20 terminal alkynes 6, 213 terminal 2,2-diorgano-l-aIkcnylboronates 51 terminal diynes 207 ternary complex 444 ternary coupling 177... 

Scheme 6-23 Tandem Heck reactions from a total synthesis of (+)-alphacalcidiol.

Scheme 6-39 Tandem Heck reaction from a synthesis of ( )-scopadulcic acid A.

The first examples of asymmetric Heck reactions (AHRs) appeared around 20 years ago, reported almost simultaneously by Shibasaki and Overman. Equations 12.47105 and 12.48106 show these first efforts. Despite the modest enantioselectivi-ties observed, the transformations are notable because they show that tertiary and especially difficult to build quaternary centers can be constructed in a stereo- and regioselective manner. Equation 12.48 also shows an example of tandem Heck reactions in which two cyclizations occur in sequence. 

The progress of tandem Heck reactions in organic synthesis [16] led to their first application in the aqueous phase. Hence, a double Heck reaction on a substrate for which /3-hydride elimination is possible results in three tricyclic products (Scheme 1) [17]. 

Highly strained ring systems can be generated from a tandem Heck reaction sequence. This achievement attests to the value of the synthetic method. ... 

Scheme 6-25 Tandem Heck reaction-phcnoxidc capture in the synthesis of opium alkaloids.

In a multifimctional process, a Rh/TPPTS system was applied besides a Pd/TPPTS system for a tandem Heck reaction/hydroformylation sequence in one pot (cf. Scheme 2). The results are described in more detail in Sect. 2.1.1.1. 

Harrowven, D.C., Woodcock, T. and Howes, P.D. (2002) A tandem Heck reaction leading to a 26-membered carbocycle. Tetrahedron Lett., 43, 9327-9. 

Garcia, A., Rodriguez, D., Castedo, L. et al. (2(X)1) Synthesis of fused rings at a pivotal nitrogen tandem Heck reactions of A-vinyl-2-iodobenzamides. Tetrahedron Lett., 42, 1903-5. 

For previous reports of tandem Heck reaction-anionic capture sequences, see (a) Grigg, R., Sridharan, V. and Xu, L.-H. (1995) Palladium-catalyzed cyclization-amination of allenes - effect of base on regioselectivity of formation of allylic amines. J. Chem. Soc., Chem. Commun., 1903 and references cited therein (b) Ma, S. and Negishi, E. (1995) Palladium-catalyzed cyclization of general route to common, medium, and large ring compounds via cyclic carbopaUadation. J. Am. Chem. Soc., 117, 6345-7 and references cited therein. 

With many appropriately constructed alkenyl halides, these homogeneous transfer hydrogenation conditions promote the reductive tandem Heck reaction to give polycyclic products. An example is shown in Scheme This useful reaction is discussed more extensively in Sect. IV.2.2. 

SCHEME 6.4 Palladium-catalyzed tandem Heck reaction/C-H activation. 

Felpin et al. developed a palladium-catalyzed tandem Heck reaction-reduction-cyclization synthesis of oxindoles (n=0) and dihydroquinolones (n= 1) using different 2-(2-nitrophenyl)aaylates (n=0) or 2-(2-nitrobenzyl)aaylates (n=l) and aryldiazonium salts 36 in good yield [15] (Scheme 6.7). However, a complementary approach was developed by the same group using diazonium salts 40 and substituted acrylates 41 to access a larger substitution pattern on the C3 position (Scheme 6.8). It is noteworthy that a different solvent was required and the charcoal had to be added after the Heck reaction. C3-unsubstituted, arylated, and alkylated dihydroquinolones 42 can be obtained efficiently using this protocol. 

SCHEME 6.7 Tandem Heck reaction/reduction/cyclization. 

SCHEME 6.8 Synthesis of dihydroquinolones by tandem Heck reaction/reduction/ cyclization. 

Szlosek-Pinaud et al. developed a very simple and efficient method for the preparation of a wide range of functionalized 3,3-disubstituted-2,3-dihydrobenzofurans 64 via palladium-catalyzed tandem Heck reaction/Suzuki cross-coupling [24] (Scheme 6.15). 

SCHEME 6.15 Tandem Heck reaction/Suzuki coupling. 

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