Cycloisomerization thermal

According to the Woodward-Hoffmann rule [6, 7], conjugate polyenes with 4n and 4n+2 n electrons undergo cychzations in conrotatory and disrotatory fashions under the thermal conditions, respectively. Recently, novel cycloisomerizations were found to be catalyzed by Lewis acid and to afford bicychc products [39] as photochemical reactions do [40]. The new finding supports the mechanistic spectrum of chemical reactions. 

However, in contrast to Fe(0)-ate complexes 38-40 (cf. Sect. 4.2), complex 67 failed to catalyze Alder-ene cycloisomerizations, which may be attributed to the thermal lability of this complex [17]. 

The [4+ 4]-homolog of the [4 + 2]-Alder-ene reaction (Equation (48)) is thermally forbidden. However, in the presence of iron(m) 2,4-pentanedioate (Fe(acac)3) and 2,2 -bipyridine (bipy) ligand, Takacs57 found that triene 77 cyclizes to form cyclopentane 78 (Equation (49)), constituting an unprecedented formal [4 + 4]-ene cycloisomerization. The proposed mechanism for this transformation involves oxidative cyclization followed by /3-hydride elimination and reductive elimination to yield the cyclized product (Scheme 18). 

Weinreb86 has reported the Alder-ene cyclization of enallenes under thermal conditions (Equation (85)). Varying the substitution pattern of alkene and allene groups had little effect on the yield of cyclized product. One exception was a,/ -unsaturated ester 130(Equation (86)) cycloisomerization under thermal conditions led to the formation of the Alder-ene product 131 and the unexpected hetero-Diels-Alder product 132 in a 3 1 ratio. 

Thermal conditions were effective in the stereoselective oxa-ene cycloisomerization of allenylsilanes, furnishing both substituted cyclopentanes and, as in Equation (88), substituted cyclohexanes. 

Although a number of competing pathways have been shown to be involved301 in the thermal cycloisomerization of hexa-l,3-dien-5-ynes (255), isobenzenes (256) have been established302 as intermediates in their thermal rearrangement to arenes. On solvolysis, the diethylphosphate ester of l-(2-ethynylphenyl)-4-trimethylsilyl-4-(trimethylsilyl-oxy)pent-2-yn-l-ol has been found303 to afford 5-(2-ethynylphenyl)-3-trimethylsilyl-... 

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... 

The alkynyl epoxide 52 cycloisomerized to a furan in the presence of a group VI transition metal catalyst <1994JA9363>. The analogous reaction with alkynyl thiirane 53 was also observed although thermal extrusion of sulfur was the major competing side reaction (Scheme 19) <2000S970>. 

There has been broad scientific interest in the synthesis of analogs of la,25-dihydrox-yvitamin D3 193 due their potential clinical applications. A concise entry into the triene-containing tricyclic core structure from simple precursors is available using an enyne cycloisomerization. The precursors of the central cascade reaction are the alkenyl bromide 188 and enyne 189, which are easily obtained in enantiomerically pure form (Scheme 29).[66].[6v] In iiie key reaction, alkenyl bromide 188 and enyne 189 are converted into a 10 1 mixture of triene 191 and the thermally rearranged product 194. After recycling of 194 to 191, a yield of 76% was reahzed. Alkenyl bromide 188 undergoes regiospecific intramolecular carbopalladation of enyne 189 to provide the dienylpalladium complex 190. 

More recently, Saito and Hanzawa demonstrated that a variety of fused, tri-, tetra-and penta-substituted indoles 190 could be efficiently accessed via the Rh(I)-catalyzed cydoisomerization of N-propargyl anilines 188 (Scheme 9.68) [225, 226]. This transformation presumably involves the initial Rh(I)-catalyzed amino-Claisen rearrangement of 188 to produce a putative reactive allenyl aniline intermediate 189, which is smoothly converted into the indole core, as exemplified by the cycloisomerization of an independently prepared allene 191 (Scheme 9.69). On the other hand, the latter transformation of allenes can be achieved under thermal reaction conditions, albeit with a diminished effidency. 

The direct reductive elimination from intermediates 2 leads to the formation of products 5 which present a very constrained structure. Usually, a con-rotatory thermal opening leads to the formation of vinylcycloalkenes 6. Only when the electrocyclic opening of the cyclobutene is not favoured, due to geometrical, steric or electronic reasons, the cyclobutene derivative can be isolated. This is the case with a substrate such as 9 which undergoes cycloisomerization via a formal [2+2] cycloaddition to give the polycyclic compound 10 (Eq. 2) [5],... 

Alder-ene reaction of l,n-enynes can be regarded as the archetypal of cycloisomerization reaction known for over 60 years in its uncatalyzed thermal form [28]. From mechanistic point of view, the reaction involves a six-electron pericyclic rearrangement between an aUylic hydrogen (the ene) and an... 

The cycloisomerization/cycloaddition cascade approach has been extended to bis (benzannulated) 5,6-spiroacetals recently by Xue et al. [166] (Scheme 80). Thus, Cu (I)-catalyzed cycloisomerization of aUcynol 327 gives the enol ether 329, which then undergoes HDA with the o-QM 330, generated in situ from 328 under flie thermal reaction conditions. The bis(benzannulated) spiroacetals 331 were obtained in good yield and selectivity (dr >20 1), favoring the doubly anomeric configuration. 

The [2-I-2-I-2] cycloaddition reaction is a pathway to construct complex molecules in a single step in an economical procedure. The potential of the transformation within the macrocyclic unit was successful and resulted in the formation of fused tetracyclic macrocycles in high yield. Thermally induced cycloisomerization that could not be initiated by metals also occurs in the case of such macrocycies. 

Gonzalez, L, Pla-Quintana, A., Roglans, A., et al. (2010) Ene reactions between two alkynes Doors open to thermally induced cycloisomerization of macrocyclic triynes and enediynes. Journal of the Chemical Society, Chemical Communications (46), 2944-2946. 

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