Heck tandem

FIGURE 1. Possible Heck-tandem product under various conditions. 

Scheme 6. Oppolzer s tandem palladium-ene/twofold Heck insertion process.

NHC-Pd(ll) complexes have also been used in tandem reactions involving a Sonogashira couphng and hydroalkoxylation of the resulting alkyne for the synthesis of benzofurans [131] as well as sequential Heck-Sonogashira couphngs [132] (Scheme 6.44). 

Scheme 6.44 Tandem Sonogashira-hydroaUcoxylation and Sonogashira-Heck reactions...

Carbonylation can also be carried out as a tandem reaction in intramolecular Heck reactions. 

A tandem palladium-catalysed ort/io-alkylation/intramolecular Heck reaction coupling sequence was used effectively to access in fair yields the tetrahydro 1-benzoxepines 67 from the iodoaryl precursor 66 and the appropriate alkyl bromide. The norbornene plays a relay role in the proposed reaction cycle <06JOC4937>... 

Figure 6.20. Tandem ring-closing metathesis and Heck coupling for the formation of bridged ring...

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],... 

This indole C-7 Heck cyclization strategy was employed by Shao and Cai in a synthesis of anhydrolycorine-7-one from the requisite N-aroylindoline [275], by Miki in syntheses of pratosine and hippadine from substrates like 262 [276], and by Rigby to synthesize anhydrodehydrolycorine from an N-benzylhydroindolone [277, 278]. Thai and co-workers constructed examples of the new ring systems, pyrido[2 ,3-d ]pyridazino[2,3-a]indole (264) and pyrido[2 ,3 -Heck cyclizations on the appropriate 2-bromopyridine precursors (e.g., 263) at C-2 or C-7, respectively [279, 280]. Compound 264 undergoes oxidative-addition with methyl acrylate at the C-3 position. This resulting product (not shown) can also be obtained from 263 in a tandem Heck sequence with methyl acrylate (62% yield). 

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],... 

The research group of Cacchi made extensive use of these tandem cyclization-Heck reactions to prepare a wide variety of indoles [311-314], For example, vinyl triflates react with o-aminophenylacetylene to afford an array of 2-substituted indoles in excellent yield, e.g., 356 to 357 [312], and a similar reaction of 358 with aryl iodides leads to an excellent synthesis of 3-arylindoles 359 [313],... 

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. 

Jorgensen, T. J. D., Hvelplund, P., Andersen, J. U., Roepstorff, P. Tandem mass spectrometry of specific vs. nonspecific noncovalent complexes of vancomycin antibiotics and peptide ligands. Int J Mass Spectrom 2002, 219, 659-670. Tahallah, N., Pinkse, M., Maier, C. S., Heck, A. J. The effect of the source pressure on the abundance of ions of noncovalent protein assemblies in an electrospray ionization orthogonal time-of-fiight instrument. Rapid... 

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>. 

Heck intramolecular cyclization. Silver carbonate or nitrate was added originally to tandem Heck arylation reactions to depress alkene isomerization, but they also improve selectivity in the -elimination step. Grigg et al.1 have used a number of useful additives such as triethylammonium chloride, sodium formate (15, 248), phenylzinc chloride, as well as silver(l) and thallium(I) salts. In fact, thallium(I) salts... 

Intramolecular Heck cyclizations.13 Pd(0)-catalyzed cyclization of substrates containing one alkenyl and one vinyl iodide group is a well-established route to bicyclic products (14, 297-298 15, 301-302). Tandem cyclization to tricyclic products is possible when the substrate contains a triple bond. Thus, in the presence of a Pd(0) catalyst and 2 equiv. of triethylamine, 1 undergoes tricyclization to 2 in high... 

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