Pd-catalyzed cycloisomerizations

The authors confirmed the formation of vinyl Ru-complex 21 by the reaction of [Cp Ru(SBu-t)]2 with methyl propiolate (Eq. 7.15). To my knowledge, this is the first observation of the insertion of an alkyne into the M-S bond within a catalytically active metal complex. In 2000, Gabriele et al. reported the Pd-catalyzed cycloisomerization of (Z)-2-en-4-yne-l-thiol affording a thiophene derivative 22 (Eq. 7.16) [26]. 

Scheme 7-3 A proposed reaction path of Pd-catalyzed cycloisomerization of (Z)-2-en-4-yne-l-thiol...

The preparation of 5-arylfurfurals (and arylthiophene-2-carboxaldehydes) via Pd-catalyzed C-C bond formation in aqueous media was carried out <990L965>. Full details have been reported for the Pd-catalyzed cycloisomerization of (Z)-2-en-4-yn-l-ols (a facile synthesis of a variety of substituted furans) <99JOC7687>... 

The picrotoxane sesquiterpenes are a family of natural products from a poisonous berry Menispermum cocculus which were documented as early as the 1600s by Indian natives who used them to stun fish and kill body lice. Trost and coworkers reported an approach to total synthesis of this family based on Pd-catalyzed cycloisomerization [68, 69]. Several synthesis recipes were tested and it was found that a combination of dbpp with a ligand capable of internal proton delivery (dpba) gave the best result and provided a key intermediate 27 for total syntheses of corianin, picrotoxinin, picrotin, and picrotoxate (Scheme 10). 

Cycloisomerizations of enynes catalyzed by Pd complexes address fundamental issues of atom-economy and have become valuable tools in synthetic organic chemistry (for leading reviews on Pd-catalyzed cycloisomerizations see [142-146]). 

Pd-catalyzed cycloisomerization of (Z)-2-en-4-yne-l-thiols 111 gives substituted thiophenes 112. The mechanism involves electrophilic activation of the alkyne moiety by Pd(ll) followed by intramolecular cyclization, protonolysis, and aromatization (Scheme 25) <20000L351>. S-Endo cyclization of alkynyl thiols 113 using a Mo, W, or Cr catalyst affords dihydrothiophene 114 <2000S970>. 

Trost BM, Romero DL, Rise F (1994) Pd-Catalyzed Cycloisomerization to 1,2-Dialkylide-necycloalkanes. 2. Alternative Catalyst System. J Am Chem Soc 116 4268... 

Finally, a few other recent developments in the area of m ramolecular alkyne cyclocoupling should be mentioned because of their considerable synthetic value, although the involvement of alkyne complexes is uncertain. These include Livinghouse s Rh-catalyzed Diels-Alder reactions [HO]. Negishi s stoichiometric Zr-promoted bicyclization of ene-ynes [97] (Scheme 4-32), and Tl-ost s Pd-catalyzed cycloisomerization of ene-ynes [111] (Scheme 4-33). 

Lewis acids as cocatalysts are effective for Pd-catalyzed cycloisomerization. The reaction of diallylmalonate 36 in the presence of AgOTf afforded 63 with high selectivity [31]. Asymmetric cyclization of 1,6-diene 36 was carried out using PdCl2(MeCN)2-AgBF4 in the presence of a chiral ligand [32]. Cycloisomerization... 

At first glance bisdiene substrates in which the two 1,3-diene subunits are substituted differently (e.g.. Scheme 6,17) appear to be improper candidates for Pd-catalyzed cycloisomerization, as they would probably lead to a mixture of isomers (e.g., 18). This is known for the linear dimerization of simple substituted 1,3-dienes (e.g., isoprene or piperylene). The attempted selective cross-coupling of different 1,3-dienes usually affords a complex mixture of isomeric products (vide infra). Nonetheless, the Pd-catalyzed cy-clization of bisdiene 17 does not form any of the isomeric 18 structures, but instead affords the single enediene 19 in near quantitative yield (95%). 

Bisdiene 35 bears a complementary substitution pattern to that of 32b that is, the benzyl substituent resides adjacent to the methyl-bearing 1,3-diene moiety. Bisdiene 35 also cyclizes smoothly under the conditions employed for 32b and affords compound 36 in high yield (95%), and with good diastereoselectivity (>90% diastereomeric purity). Thus, bisdienes bearing an ester substituent undergo facile Pd-catalyzed cycloisomerization via a pathway that complements that found for substrates without the ester substituent. This defines a new bond construction that is inaccessible by classical... 

Functionalized benzo[b]furans 27 are formed by Pd-catalyzed cycloisomerization of (o-hydroxyphenyl)-substituted propargyl alcohols 25 leading to enol ethers 26 followed by acid-catalyzed allyhc rearrangement with solvent incorporation (26 — 27) [50] ... 

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