Heck reaction tandem reactions

Sonogashira/nucleophilic addition (Scheme 7.34) [70], The reaction started by the Ugi-4CR, giving the intermediate 82, which was transformed into the enyne 83 by a Heck-Sonogashira tandem reaction. Finally, the activated enyne evolved an aza-Michael-type addition to give the final six-component product 84. 

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>... 

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],... 

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. 

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>. 

Tandem Radical Cyclization/Cross-Coupling or Heck Reactions... 

Tandem Radical 5-exo Cyclization/Heck Reactions or Tandem Radical Cyclization/Allylic Substitution Reactions... 

Oshima s group reported the first example of a tandem radical cyclization/intermo-lecular Heck reaction in 2002 (Fig. 60) [289]. Iodoacetaldehyde allyl acetal 242a was treated with styrene 243, catalytic amounts of CoCl2(dpph), and trimethylsi-lylmethylmagnesium chloride 224 as a stoichiometric reducing agent. 4-Cinnamyl-butyrolactol 244 was isolated in 50% yield (cf. Fig. 54). 

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