Cycloisomerism

Palladium catalyzed cycloisomerizations of 6-cn-l-ynes lead most readily to five-membered rings. Palladium binds exclusively to terminal C = C triple bonds in the presence of internal ones and induces cyclizations with high chemoselectivity. Synthetically useful bis-exocyclic 1,3-dienes have been obtained in high yields, which can, for example, be applied in Diels-Alder reactions (B.M. Trost, 1989). 

Another possibility is observed upon cyclization of hydrazides of pyrazole-carboxylic acids in the presence of CuCl in an inert atmosphere in DMF. When acetylenylcarboxylic acids are heated in the presence of CuCl in DMF, the orientation of the cycloaddition of the hydrazide group differs from that observed for cyclization in basic conditions. The cycloisomerization of hydrazides 78 in boiling DMF leads to the corresponding pyrazolopyridazines 79 in 60-71 % yields (Scheme 134 Table XXIX) (85IZV1367 85MI2). 

The cycloisomerization of hydrazide 80, catalyzed by CuCl, gives diazine 81, 5-Ai-aminolactam 82, and, unexpectedly, 6,7-dihydro-4-vinyl-1-methylpyrazolo [3,4-if]pyridazine-7 83 (85MI2) (Scheme 135). 

Scheme 19. Photochemical A-D cycloisomerization presumed reaction path.

Another useful class of palladium-catalyzed cycloisomerizations is based on the general mechanistic pathway shown in Scheme 13. In this chemistry, a hydridopalladium acetate complex is regarded as the catalytically active species.27b-29 According to this pathway, coordination of a generic enyne such as 59 to the palladium metal center facilitates a hydropalladation reaction to give intermediate 60. With a pendant alkene, 60 can then participate in a ring-form-... 

Scheme 13. Trost s hydridopalladium acetate catalyzed cycloisomerization chemistry.

Although the conversion of 63—>67 adequately expresses the utility of palladium-catalyzed cycloisomerizations for the construction of complex polycycles, the single-step, palladium-mediated conversion of compound 68 to the novel polyspirocycle 6930,31 (Scheme 15) can perhaps be regarded as the paragon of this chemistry. In this striking transformation, chemo- and regioselective... 

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

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. 

Next to cycloisomerizations, catalysts like 11 are also useful for [4 + 2] and even more interesting for [5 + 2] cycloaddition reactions (Fig. 11), which are very... 

A so far unsolved problem is the development of asymmetric procedures for the above described Fe(0)-catalyzed cycloisomerizations and cycloadditions. The option to use the element of planar chirality might allow to successfully address this issue in future applications. 

Fiirstner A, Martin R, Majima K (2005) Cycloisomerization of enynes catalyzed by iron (0)—ate complexes. J Am Chem Soc 127 12236-12237... 

Fiirstner A, Majima K, Martin R, Krause H, Kattnig E, Goddard R, Lehmann CW (2008) A cheap metal for a Noble task preparative and mechanistic aspects of cycloisomerization and cycloaddition reactions catalyzed by low-valent iron complexes. J Am Chem Soc 130 1992-2004... 

Complex 38 also turned out to be an efficient catalyst for cycloisomerization reactions of enynes 41 (Scheme 8) [16, 17]. This seems reasonable if one considers the fact that Fe(0) is isoelectronic to Rh(+1), which is also a catalyst for Alder-ene cycloisomerizations [18, 19]. 

Scheme 8 Catalytic role of iron in cycloisomerization reactions [17]...

With regard to the mechanism of the cycloisomerization, Fiirstner et al. found strong evidence of a metallacyclic intermediate. By labeling the allylic position of enynes 46 and 48, they showed that reactions yielding traws-annulated rings 47 transferred the deuterium atom to the exocychc double bond (eq. 1 in Scheme 10), whereas c -annulated rings 49 formed with complete preservation of the position of the deuterium atom (eq. 2 in Scheme 10). This corresponds well to a metallacycUc... 

Similar to this cycloaddition, ferrate 40 also proved to be catalytically active in [5 + 2]-cycloadditions, as discussed for ferrate 38 (eq. 2 in Scheme 11). As for the cycloisomerization reactions, ferrate 40 also turned out to be reactive toward... 

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 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...

In addition to the reactions discussed above, there are still other alkyne reactions carried out in aqueous media. Examples include the Pseudomonas cepacia lipase-catalyzed hydrolysis of propargylic acetate in an acetone-water solvent system,137 the ruthenium-catalyzed cycloisomerization-oxidation of propargyl alcohols in DMF-water,138 an intramolecular allylindination of terminal alkyne in THF-water,139 and alkyne polymerization catalyzed by late-transition metals.140... 

Silane reduces the palladium acetate in 119 to the palladium hydride 120, which undergoes reductive elimination to provide the organic product and the catalytic Pd(II) species. This mechanistic hypothesis was supported by the use of EtsSiD as the reductant product was formed with D incorporation at only the methyl group [70]. This reaction is best performed with a Pd(0) precatalyst in the presence of acetic acid and 10 eq. of silane, which suppresses the competitive cycloisomerization reaction [70]. 

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