Cycloisomerization and Related Reactions

Csscade Heck Reaction. Besides cycloisomerization and related reactions, Pd(0) species also catalyzes cascade Heck reactions, which offer attractive routes to a wide variety of polycyclic compounds (99-101). For example, pyra-nosides 107 has been synthesized through 5-exo trig double Heck annulation of bromo-diene 106 in the presence of a catalytic amovmt of Pd(OAc)2 and PPha (Scheme 54) (102). 

The fact that cycloisomerization and related reactions provide a mild method for carbon-carbon bond formation, with the need for strong acids and bases, is further demonstrated by the fact that another of these reactions was used earlier in the same synthesis to combine alkyne 11.285 with alkene 11.284 to give the pyran 11.286 (Scheme 11.95). 

Trost BM (1990) Palladium-catalyzed Cycloisomerizations of Enynes and Related Reactions. Acc Chem Res 23 34... 

Trost, B. M. Palladium-catalyzed cycloisomerizations of enynes and related reactions. Acc. Chem. Res. 1990, 23, 34-42. 

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. 

The corresponding reaction of but-3-yn-l-ols or pent-4-yn-l-ols with primary or secondary alcohols in the presence of catalytic amounts of Ph3PAuBF4 and p-TsOH afforded tetrahydrofuranyl ethers (Scheme 4-76). This tandem 5-endo-cycloisomerization/hydroalkoxylation proceeds via 2,3-dihydrofurans, which then undergo an intermolecular Bronsted acid-catalyzed addition of the external alcohol. The transformation is not restricted to internal alkynols but can be applied to terminal acetylenes as well. Application of the method to the s thesis of bicyclic heterocycles with a P-lactam structure was reported recently.Under the same conditions, epoxyalkynes undergo a sequence of epoxide opening, 6-exo-cycloisomerization, and nucleophilic addition to afford tetrahydropyranyl ethers. In a closely related transformation, cyclic acetals were obtained from alk-2-ynoates bearing a hydroxy group in 6- or 7-position by treatment with AuCU and MeOH. ... 

Cyclization of 2-benzylpent-4-enoic acid (a-benzyl-a-allylacetic acid) and related compounds 1 to corresponding 1,2,3,4-tetrahydronaphthalene (tetralin) derivatives 2, catalyzed by a strong acid, has been called Darzens synthesis of tetralin derivatives. The reaction formally falls into the category of a cycloisomerization reaction of alkenyl-substituted arenes. 

In 2012, Vanderwal group reported two strategies for the short synthesis of echinopine B, both relying on platinum-catalyzed cycloisomerization closely related to Chen synthesis enynes 112 and 113 (Scheme 7.64) [92]. In each case, the group isolated fair amounts of by-products attributed to the different cycloisomerization modes of platinum chloride reaction (Scheme 7.65). 

A related reaction to hydration of alkynes is intramolecular addition of alcohols to a triple bond. This reaction was used for cycloisomerization of homo-propargyl alcohols to the butyrolactones 79 and it was catalyzed by the ruthenium complex (rj -C5H5)Ru(COD)Cl 78 in a combination with tris(furyl) phosphine (TFP), an ammonium salt and an oxidant (NOHS=iV-hydroxysuc-cinimide) (Scheme 31). 

Dankwardt s vinylidene-mediated reaction apparently operates concurrently with cationic cycloisomerization to give 3-silyl-l-silyloxy naphthalenes (e.g., 13). From his data, a direct comparison can be made of the effect of different metal complexes and silyl groups on selectivity for a vinylidene-mediated reaction pathway (Table 9.2). At least in this instance, Rh(I) is more vinylidene friendly than Pt(II). Iwasawa and coworkers [7], in an isolated related report, also obtained high selectivity for silyl-shifted products in the presence of a Rh(I)-catalyst, albeit one with a substantially different ligand set from that employed by Dankwardt. 

Cycloisomerization or metathesis also occurs, which can be understood as the formation of cyclobutene 326 by reductive elimination of 321. The metathesis product 327 is formed by isomerization of 326. The metatheses involving metal-carbene complexes are discussed in Section 7.2.6. They are closely related, but somewhat different from the metathesis explained here. Balance between the ene and the metathesis reactions seems to be delicate. 

Our interest in this chapter is in silver-catalyzed cycloisomerization reactions. Therefore, we shall present different silver-catalyzed cycloisomerization reactions as a function of the nucleophilic and electrophilic moiety. Cycloisomerization reactions including the classical ene-yne cycloisomerization (with X = CHR, Scheme 5.1), and the related heterocyclization reactions with heteroatoms embedded in unsaturated systems (X = NR, O Scheme 5.1) belong to the same reaction family. In addition, the alkynyl part can be exchanged for an allene unit. Internal or external nucleophiles (Nu) can then stabilize, through cascade reactions, the positive charge created.24... 

Finally, the cycloisomerization of 4-vinylcyclohexene (a butadiene dimer) to bicyclo[3.3.0]-2-octene (6) was found to occur at 250° over a silicophosphoric acid catalyst (11), along with a very large amount of hydrogen transfer (ethylcyclohexenes, methylethylcyclopentenes, ethylbenzene) and polymerization, a reaction closely related to that of limonene (5). A much better yield of the same hydrocarbon (6) was obtained from 1,5-cyclooctadiene (72% at 200°) with the same catalyst (25). 

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