Suzuki reaction intramolecular coupling

For the domino transition metal-catalyzed synthesis of macrocycles, conditions must be found for two distinct cross-coupling reactions, of which one is inter- and the other intramolecular. For this purpose, Zhu s group [115] has developed a process of a Miyura arylboronic ester formation followed by an intramolecular Suzuki reaction to give model compounds of the biphenomycin structure 6/1-232 containing an endo-aryl-aryl bond. 

A series of 2-aryloxazoloquinolones 32 having high affinity for the GABA receptor were prepared via a Pd-catalyzed intramolecular diaryl coupling of ethyl 5-bromo-2-phenyl-oxazole-4-carboxylate with 2-aminophenylboronic acid followed by cyclization [37]. This one-pot intramolecular Suzuki reaction was followed by cyclization to afford a tricyclic compound 32. 

Intramolecular coupling of 120 having an aryl iodide group and a vinylstannane group accomplished the total synthesis of (-)-zealarenone (99) (Scheme 19) [77]. The first total synthesis of macrolactin A (124) was efficiently accomplished based on the Stille reaction of 122 for both stereospecific construction of the diene moieties and closure of the 24-membered macrocyclic ring [78]. The key precursor 122 was synthesized via two Stille couplings and Mitsunobu esterification. An alternative route to the dimethyl ether 125 was reported by cyclization of 123, which was prepared by the Stille and Suzuki couplings followed by DCC-DMAP esterification... 

A more sophisticated procedure has recently allowed the preparation of palladium complex 34, based on an intramolecular Suzuki coupling. The key intermediate 39 is generated by oxidative addition of palladium(O) to 38, and treatment of 39 with base promotes a Suzuki-type intramolecular reaction leading to 34 (Scheme 7) [26]. The same procedure is applicable to the synthesis of benzyne-nickel complexes with a variety of ligands (PPh3, PCy3, PEt3) [26]. 

Several unusual silametacyclophanes, macrocyclic cage compounds, have been prepared by multiple Pd(0)-catalyzed Suzuki coupling reactions of 9-BBN adducts of allylsilane and bromobenzene. For example, reaction of 9-BBN adduct of methyltriallylsilane and 1,3,5-tribromobenzene leads to 4-methyl-4-sila[3 - ][7] metacyclophane, 4-(2-propenyl)-4-methyl-4-sila[7]metacyclophane, which results from an intramolecular coupling of two legs of the silane and -elimination of the third leg and 4-(3-phenylpropyl)-4-methyl-4-sila[7]metacyclophane (Eq. 

Homoallylic alcohol 9 is readily prepared by palladium-catalyzed directed cyanoboration followed by Suzuki-Miyaura cross-coupling (Scheme 5.15) [15]. Palladium-catalyzed allyl transfer from 9 to aryl bromide results in removal of the hydroxymethyl directing group and concomitant formation of 3,4-diaryl-2-butenenitrile albeit the lack of regio- and stereospecificity. The overall transformation proposes a concept of intramolecular reaction with a carbon tether removable through retro-allylation. 

Treatment of a benzyl-substituted and symmetrical bis-enol tri-flate with various aryl boronic acids in the presence of Pd(OAc)2 results in a Suzuki-Miyaura cross-coupling reaction, then an intramolecular Heck reaction between the remaining triflate residue and the benzyl group and so as to give the illustrated product (eq 96).i i... 

A recent example of the application of solid phase Suzuki reactions to the synthesis of pharmaceutically important biaryl compounds was shown by Nielsen et aL [115]. A range of aryl-substituted pyrroloisoquinolines were synthesized from biarylalanine precursors in high purity (Scheme 39). This involved a Suzuki coupling of sohd-supported iodophenylalanine derivatives containing a masked aldehyde to various boronic acids, followed by hberation of the aldehyde, TFA-mediated intramolecular Pictet-Spengler reaction, and cleavage. 

An enantioselective total synthesis of (+)-phomactin A (181) has been recently reported by Halcomb using intramolecular Suzuki coupling of a B-alkyl-9-BBN derivative to prepare the macrocycle in the final step [162,163], Thus, a regioselective hydroboration of the terminal olefin in the precursor 182 gave an internal alkyl-borane that was cyclized using modification of Johnson s conditions [164], The reaction illustrates the mildness of the Suzuki reaction since the coupling was carried out in the presence of the sensitive dihydrofuran ring (Scheme 3.95). 

Brick et al. have studied this bromination in more detail and showed that the extent of the bromination can be controlled by changing the ratio of the reagents. The first substitution was found to be in the para position but subsequent intramolecular rearrangements allowed the formation of 2-5-dibrominated species. Brick et al. also reported the functionalization of such species using Pd-catalyzed reactions such as Heck and Suzuki couplings to give fully substituted p-stilbenes, p-biphenyls, diarylamines, and methylcinnamates. Hydrogenation of... 

Another Suzuki coupling reaction was described by Zhang et al., to produce arylindoles 116a and b, using solid-phase synthesis [76]. The synthesis was achieved by palladium-mediated coupling/intramolecular indole cycli-zation of resin-bound 2-trimethylsilylindole 117, Scheme 29. 

In order to introduce functionality at key positions, an intramolecular Diels-Alder reaction with furan as the diene component was planned. Suzuki coupling of the previously mentioned 105 with furan-3-boronic acid 106 gave compound 107, which was N-tosylated to 108. Construction of the dienophile portion was performed as in the previous case, by addition of vinylmagne-sium bromide to give 109, followed by MnC>2 oxidation to give the cyclization precursor, which was immediately heated at 120 °C in toluene and afforded compound 110, which incorporates an oxygen atom at both the ketone and vinyl chloride positions of welwistatin (Scheme 24). 

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