Aryl triflates cyclization

Palladium-catalyzed arylation of olefins and the analogous alkenylation (Heck reaction) are the useful synthetic methods for carbon-carbon bond formation.60 Although these reactions have been known for over 20 years, it was only in 1989 that the asymmetric Heck reaction was pioneered in independent work by Sato et al.60d and Carpenter et al.61 These scientists demonstrated that intramolecular cyclization of an alkenyl iodide or triflate yielded chiral cyclic compounds with approximately 45% ee. The first example of the intermolecular asymmetric Heck reaction was reported by Ozawa et al.60c Under appropriate conditions, the major product was obtained in over 96% ee for a variety of aryl triflates.62... 

Fagnou et al. reported the synthesis of mukonine (11) starting from methyl vanillate (644). This synthesis uses both a palladium(0)-catalyzed intermolecular direct arylation and an intramolecular cyclization reaction. Triflation of methyl vanillate (644) afforded the aryl triflate 645. Using a Buchwald-Flartwig amination protocol, the latter was subjected to direct arylation with 2-chloroaniline (646) to furnish the corresponding diarylamine 647. Finally, intramolecular cyclization of 647 afforded mukonine (11). To date, this is the best synthesis (three steps, 75% overall yield) available for mukonine based on commercially available methyl vanillate (644) (582) (Scheme 5.45). 

With (i ,i )-BINAP as the ligand, Keay and Lau have been able to achieve the cascade cyclizations of the dienyl-substituted aryl triflates 134 toward the total synthesis of the natural product (+)-halenaquinone with ee s of up to 96% (Scheme 35). For these substrates, they observed an interesting influence of the remote substituent in 134. ... 

Shibasaki and co-workers have described a regioselective Heck cyclization of aryl triflate 12.1, which ultimately provides tricyclic enone 12.4, a key intermediate in a number of diterpene syntheses (Scheme 8G.12) [25], Treatment of 12.1 under typical cationic conditions resulted in preferential 6-exo closure to give 12.2 and 12.3 as a 3 1 mixture in 62% overall yield and with 95% ee for both products. The complete selectivity for 6-exo cyclization is noteworthy because 6-endo, 5-exo, and 7-endo cyclization modes were also possible. An analysis of the steric interactions involved in the various cyclization modes was presented and was used to rationalize the observed selectivity. Non-conjugated diene 12.2 could be isomerized to the fully conjugated diene 12.3 in quantitative yield by using catalytic naphthalene Cr(CO)3. Both Heck products could be converted to the enone 12.4,... 

The analogous Z aryl triflate 19.1 reacts under the cationic manifold to give, ultimately, oxindole (/ )-17.3a in 72% yield and 43-48% ee (Scheme 8G.19) [38]. An important synthetic advance is the observation that Heck cyclization of this substrate could be diverted to the more selective neutral pathway by addition of halide salts. For example, Heck cyclization of triflate 19.1 in the presence of 1 equiv. of n-Bu4NI gave (/ )-17.3a in 62% yield and 90% ee, which is similar to the enantioselectivity obtained for cyclization of the corresponding iodide 18.1c under neutral conditions (see entry 6, Table 8G, 1). Conversely, cyclization of iodide 18.1c in the... 

Hu et al. [104] disclosed that the spiro phosphine oxide ligand (/ )-30a is highly efficient for the Pd-catalyzed Heck reaction of cyclic and heterocyclic olefins with aryl triflates. An asymmetric domino Heck cyclization was established using catalyst Pd/(/ )-30a to form fused carbo- and heterocycles with excellent stereoselectivity (Scheme 42) [105]. This method was used in a short synthesis of (-)-martinellic acid, a primary ingredient in traditional eye medicine in South America. 

One further example of quaternary center formation by AHR has been reported, this being the conversion of the aryl triflate 96 to a 3 1 mixture of the tricycHc compound 97 and its isomer 98, both of which can be converted to the enone 99, a key intermediate in the syntheses of kaurene 100 and abietic acid 101 (Scheme 28) [77,78]. Compound 97 can also be quantitatively isomerized to 98. The essentially complete selectivity towards 6-exo cyclization is noteworthy. The authors rationaUze this on the basis of unfavorable steric interactions in the alternative intermediates. 

It is well known that transition metal-catalyzed carbon-carbon bond formations are extraordinarily difficult with sterically hindered, electron-rich aryl triflates.However, just such a transformation was required to install the Z-propenyl fragment necessary for the samarium-mediated cyclization. Lauren s initial attempts to achieve this goal afforded predominantly detriflated material and capricious reactions leading to loss of biaryl enantiopurity. 

Liang, S. and Paquette, L.A. (1992) Palladium-catalyzed intramolecular cyclization of vinyl and aryl triflates. Associated regioselectivity of the 8-hydride ehmination step. Acta Chem. Scand., 46, 597-605. 

Finally, the same group carried out a mono and a double annulation of arynes to synthesize fluoren-2-ones 60 and polycyclic aromatic systems 62 respectively [40]. These methods involve the in situ formation of highly reactive arynes by reaction of 2-(trimethylsilyl)aryl triflates 58 and CsF. In the presence of Pd(dba)2 (dba = dibenzylideneacetone), a crosscoupling and cyclization with a 2-halobenzaldehyde occur in the former case and C—H activation and cyclization occur in the latter case (Scheme 8.13). 

Six-membered rings, particularly those with highly substituted benzylic stereocentres, are readily assembled by the asymmetric intramolecular Mizoroki-Heck reaction. In a seminal example, Shibasaki and coworkers [45] showed that (i )-alkenyl aryl triflate 75 can be cyclized in high yield with modest enantioselectivity to bicycle 76 (Scheme 12.18). 

The reaction has also been applied in another intramolecular version in which a cyclization occurs in the amination step (Scheme 11.4) [45]. With the use of chiral ligands, an enantioselectivity of up to 80% ee was achieved. For example, with ligand 21, the dieneamine 22, and aryl triflates 23a,b gave the corresponding products, 24a,b with 70 and 77% ee, respectively. 

Synthesis of Tetraarylporphyrins. Triflyl chloride was used under aerobic oxidation conditions to produce tetraarylporphyrins from pyrrole and various aromatic aldehydes. The reaction proceeds through condensation of pyrrole to the aromatic aldehyde to form an intermediate aryl triflate which then undergoes polymerization and cyclization of the tetrapyrrolic oligomer. Air oxidation of the porphyrinogen intermediate completes the sequence (eq 15). 

When the coupling reactions of vinyl and aryl triflates are carried out in the presence of carbon monoxide and LiCl, good yields of the cross-coupled ketones are obtained (eqs 3 and 4). This is a particularly attractive route to divinyl ketones which are important substrates in the Nazarov cyclization. 

This constitutes a pentamolecular queuing process and produces mixtures of diastereomers (5 1). Finally, a series of pentamolecular queuing cascades emplo3ung aryl (triflate, iodide) and vinyl (bromide, triflate) as starter species and carbon monoxide, al-lenes as relay species have been achieved (eq 90). The strategy employed in these cascades is analogous to that in eq 88 in which the initial oxidative product undergoes CO insertion in preference to a 4-exo-trig cyclization. 

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