Cycloisomerization approaches

Scheme 14. Trost s approach to [3.3.3]propellane 67 by hydridopalladium acetate-catalyzed sequential cycloisomerization.

This reaction is now well understood, including its stereochemical features.209 242 It should be noted that six-membered rings can be formed besides five-membered rings through this pathway, and their formation is facile with the catalytic system Pd(ll)-Pd(rv). All of these set the stage for numerous synthetic applications, such as cycloisomerization [4 + 2] tandem processes,243 and the enantioselective approach to the total synthesis of potent antiulcerogenic cassiol 247 (Scheme 62).244... 

Allenylimines 186 are not easily accessible, and the most elegant approach is the reaction of alkynylimines 185 with triethylamine to generate 186 in situ the copper ) catalyst which is also present then catalyzes the cycloisomerization to the pyrrole 187 (Scheme 15.59) [120]. The method also is applicable to the imine substructure in 2-alkynylpyridines and related substrates, thus opening up a very elegant access to condensed aromatic nitrogen heterocydes. 

Cycloisomerization represents another approach for the construction of cyclic compounds from acyclic substrates, with iridium complexes functioning as efficient catalysts. The reaction of enynes has been widely studied for example, Chatani et al. reported the transformation of 1,6-enynes into 1-vinylcyclopentenes using [lrCl(CO)3]n (Scheme 11.26) [39]. In contrast, when 1,6-enynes were submitted in the presence of [lrCl(cod)]2 and AcOH, cyclopentanes with two exo-olefin moieties were obtained (Scheme 11.27) [39]. Interestingly, however, when the Ir-DPPF complex was used, the geometry of olefinic moiety in the product was opposite (Scheme 11.28) [17]. The Ir-catalyzed cycloisomerization was efficiently utilized in a tandem reaction along with a Cu(l)-catalyzed three-component coupling, Diels-Alder reaction, and dehydrogenation for the synthesis of polycyclic pyrroles [40]. 

Parker has outlined an elegant, enantioselective synthesis of L-vancosamine derivatives commencing from noncarbohydrate precursors (Scheme 17.38) [116]. This approach features a diastereoselective allenylstannane addition and W(CO)5-catalyzed cycloisomerization to construct the pyranose core. Oxidative cyclization of the C4-carba-mate 128 is performed with 10 mol% Rh2(OAc)4 and proceeds stereospecifically to give the crystalline oxazolidinone 129 (86%). All told, synthesis of this useful L-vancosa-mine glycal equivalent covers seven steps from (S)-(-)-ethyl lactate 127 and is accomplished in 44% overall yield. 

Chiral carbo- and heterocycles are widespread structural motifs in biologically active compounds. The cycloisomerization of 1,6-dienes (A) offers an elegant and atom-economic [56] approach to five- or six-membered carbo- or heterocycles [57]. Metal complexes based on Pd [58], Ni [59], Rh [60], Ru[61], and Ti[62] have been identified as promising lead structures for catalyst development. Some of the reported systems are highly chemo- and regioselective toward the formation of the individual five-membered ring compounds B-D (Scheme 2.1.5.2). Enantioselec-tive cycloisomerization, however, has been assessed only sparsely so far, and remains a challenging task [46, 63]. 

Jt-allyl complex can be generated after cyclization, as suggested by Takacs in a Fe(0)-catalyzed cyclization of polyenes. It also can be preformed if an active functional group is present in the allylic position. The palladium-catalyzed intramolecular cycloisomerization reaction of allylic acetates is an efficient method for constructing five- or six-membered rings [56, 57]. An asymmetric approach to this transformation has been studied and so far only poor enantioselectivity has been achieved (0-20% ee) [58]. Very recently, Zhang et al. also reported a Rh-catalyzed cycloisomerization involving a Jt-allylrhodium intermediate formed from an allylic halide [59]. 

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). 

Another important approach to the synthesis of helicenes is the convergent route based on energy-rich cis.cis-dienetriynes and their Ni(0)-catalyzed [2+2+2]-cycloisomerization, which was reported by Stara and coworkers [82, 83]. The potential of this methodology was demonstrated by the synthesis of functionalized... 

Abstract This review gives an insight into the growing field of transition metal-catalyzed cascades. More particularly, we have focused on the construction of complex molecules from acyclic precursors. Several approaches have been devised. We have not covered palladium-mediated cyclizations, multiple Heck reactions, or ruthenium-catalyzed metathesis reactions because they are discussed in others chapters of this book. This manuscript is composed of two main parts. In the first part, we emphasize cascade sequences involving cycloaddition, cycloisomerization, or ene-type reactions. Most of these reaction sequences involve a transition metal-catalyzed step that is either followed by another reaction promoted by the same catalyst or by a purely thermal reaction. A simple change in the temperature of the reaction mixture is often the only technical requirement to go from one step to another. The second part covers the cascades relying on transition metalo carbenoid intermediates, which have recently undergone tremendous... 

J. Marco-Contelles, C. Destabel, P. Gallego, J. L. Chiara, and M. Bemabe, A new synthetic approach to the carbocyclic core of cyclopentane-type glycosidase inhibitors Asymmetric synthesis of amino-cyclopentitols via free radical cycloisomerization of enantiomerically pure alkyne-tethered oxime ethers derived from carbohydrates, J. Org. Chem., 61 (1996) 1354-1362. 

Trost BM, Haffner CD, Jebaratnam DJ, Krische MJ, Thomas AP (1999) The Palladium-Catalyzed Enyne Cycloisomerization Reaction in a General Approach to the Asymmetric Syntheses of the Picrotoxane Sesquiterpenes. Part. I. First-Generation Total Synthesis of Corianin and Formal Syntheses of Picrotoxinin and Picrotin. J Am Chem Soc 121 6183... 

Hashmi et al. have developed a short and high-yielding synthetic approach towards functionalized indoline derivatives 227 following a reaction sequence that consists of a three-component aza-MBH reaction from furfural catalyzed by La(OTf)3 in combination with 3-HDQ, a simple sulfonamide propargylation and a gold-catalyzed cycloisomerization (Scheme 1.86). ... 

Inspired by the elegant approach developed by Stara, Stary, and coworkers (08JOC2074, 11EJ03849, 12AGE5857) for the synthesis of [ ]-heterohelicenes, Marinetti, Voituriez, and coworkers reported in 2014 the preparation of a new series of enantioenriched [6]-oxahelicenes 84 in which the terminal helical sequence ends with a phosphole oxide (14CC2199). The synthesis starts from the phosphindoles 82 and involves a metal-mediated diastereoselective [2+24-2] cycloisomerization of optically pure aromatic triynes 83 as a key step (Scheme 22). Under optimized... 

Recently, a novel approach for the synthesis of highly substituted furans vas developed by Larock and covrorkers (Scheme 8.37). It vas reported that 2-alkynyle-nones [151-153] 93 undervrent a facile transition metal-catalyzed cycloisomerization affording highly substituted furans 94 in the presence of the external O- or electron... 

Recently, Yamamoto extended the cycloisomerization-1,3-migration approach toward the construction of indole cores possessing a C3-sulfonyl group. Thus, cydoisomerization of ortho-alkynylsulfonamides 146 occurred in the presence of Au(III)-catalyst to produce 3-sulfonylindoles 147 via a 1,3-migration of a sulfanyl group (Scheme 9.55) [216]. The proposed mechanism is similar to that reported for... 

Addressing the allenylpyridine instability problem, Gevorgyan developed the Cu(I)-catalyzed cycloisomerization of conjugated alkynyl imines 317, perfect allene 318 surrogates, as an alternative route for the construction of indolizine and other pyrrole-fused cores 319 (Scheme 9.110) [291-293]. This protocol proved to be very general and efficient for the synthesis of a variety of diversely functionalized C3-substituted heterocycles 319. On the other hand, this approach was not applicable... 

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