Heck tandem asymmetric

Tandem Asymmetric Heck and Pd-Allyl Cation Reactions... 

With this step accomplished as desired, probes of the key step of the sequence, the tandem asymmetric Heck reaction, could now commence in earnest. Based on several years of intensive research in developing appropriate systems to accomplish asymmetric Heck reactions with the ability to form all-carbon quaternary carbon centers, the Overman group expected that the exposure of 10 to a 1 2 mixture of Pd(OAc)2 and (/ )-BINAP would lead to the desired... 

Scheme 17 Tandem asymmetric allylic alkylation and intramolecular Heck coupling...

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

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. 

Scheme 5.4 Example of a tandem Heck asymmetric dihydroxylation reaction.

An asymmetric polyene cyclisation (asymmetric tandem Heck) has been reported in the synthesis of the pentacyclic polyketide (-l-)-xestoquinone. ... 

Scheme 5.11. Tandem Heck-asymmetric dihydroxylation catalyzed by NAP-Mg-PdOs bifunctional catalyst.

In a narrower sense, this review covers intramolecular Mizoroki-Heck [1] reactions forming carbocycles [2] that is, the palladium-catalyzed intramolecular coupling of vinyl/aryl (pseudo-)halides with an alkene tethered by a hydrocarbon chain. Ring closures furnishing heterocycles are covered in Chapter 6 also beyond the scope of this chapter are the domino/cascade or tandem (Chapter 8) and asymmetric processes (Chapters 12 and 16) dealing with formation of a carbocycle. 

Cheung, W.S., Patch, R.J. and Player, M.R. (2005) A tandem Heck-carbocychzation/Suzuki-coupling approach to the stereoselective syntheses of asymmetric... 

In the years since the first reports in 1989 [4,5], the scope of the asymmetric intramolecular Mizoroki-Heck reactions has been substantially increased. This transformation has now been employed as a key strategic step in total syntheses of a wide variety of polycyclic natural products. Among the features that contribute to the broad utility of asymmetric Mizoroki-Heck cyclizations are the high functional group tolerance of palladium(O)-catalysed reactions, the remarkable capacity of this transformation to forge C—C bonds in situations of considerable steric congestion and the ability to orchestrate cascade or tandem processes that form multiple rings. 

In another beautiful application, Overman et al. developed the total synthesis of the natural product (+)-minfiensine (130), having a l,2,3,4,-tetrahydro-9a,4a-(iminoethano)9H-carbazol core (Scheme 7.29) [80]. The key step in their synthesis is a tandem process consisting of a catalytic asymmetric Mizoroki-Heck ring closure and an N-acyliminium ion cyclization of dienyl carbamate triflate 127 (127—>128). The reaction proceeded smoothly using the Pfaltz ligand (S)- Bu-PHOX (85), providing (dihydroiminoethano)carbazole 129 after the addition of excess trifluoroacetic acid, with 75% overall yield and 99% enantiomeric purity (127 129). 

N. Sharma, A. Sharma, A. Shard, R. Kumar, Saima, A. K. Sinha, Chem. Eur. J. 2011, 17, 10350-10356. Pd-catalyzed orthogonal Knoevenagel/Perkin condensation-decarboxyl-ation-Heck/Suzuki sequences tandem transformations of benzaldehydes into hydroxy-fimctionalized antidiabetic stil-bene-cinnamoyl hybrids and asymmetric distyrylbenzenes. 

Although the Heck reaction mainly involves the formation of bonds between sp -hybridized carbon atoms, there are asymmetric versions. One approach is to capture the chirality of the insertion intermediate by ensuring the p-hydride elimination either occurs away from the site of the original alkene (Scheme 5.35), or is pre-empted by a different step such as another insertion in a tandem process. Another approach is to provide a symmetrical substrate with two enantiotopic alkenes (Scheme 5.36), an approach also used in metathesis chemistry (Section 8.3.6). In all of these reactions, the source of chirality is from the employment of chiral ligands for the palladium catalyst, often chelating bisphosphines. 

Early in 2003, Choudary et al. studied the catalytic activity of a unique tri-functional heterogeneous catalyst system consisting of palladium, osmium, and tungsten species for tandem Heck olefination followed by asymmetric dihydro>ylation reaction induced by cinchona alkaloid (DHQD)2PHAL in the presence of a tertiary amine such as N-methylmorpholine (NMM) in one pot. The trimetal catalyst system of Pd-Os-W was embedded into hexagonal layered double-hydroxides (LDHs). As shown in Scheme 7.57, the corresponding almost enantiopure diol was achieved in high yield. This remarkable result was not clearly understood by the authors. 

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