Hydroarylation intramolecular

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

The intramolecular hydroarylation/cyclisation of aryl propargylic acetates catalysed by the system [AuCl(IPr)]/AgBF (1 1, 2 mol%, 72-92%, rt, 5 min) was developed as a versatile and efficient method leading to indene derivatives 110 (Scheme 2.20). Analogous catalytic systems, where the IPr was substituted by PPh, gave lower conversions and chemo-Zregio-selectivity. 

Scheme Z20 The synthesis of substituted indenes by intramolecular hydroarylation of aryl prop-argytic acetates...

Coumarins are formed by the intramolecular hydroarylation of an activated alkyne. The basic starting materials for this fast, efficient and general Pd-catalysed reaction are phenols and alkynoic acids (Scheme 42), An intermolecular version in which electron-rich phenols react with 4-methoxycinnamic acid leads to high yields of 3,4-dihydrocoumarins... 

Similar intramolecular hydroarylations of alkynes and alkenes, which obviate the need for a halide or triflate group on the aryl ring, are now well established. Sames group screened over 60 potential catalysts and over 200 reaction conditions, and found that Ru(m) complexes and a silver salt were optimal. This process appears to tolerate steric hindrance and halogen substrates on the arene (Equations (175)—(177)). The reaction is thought to involve alkene-Ru coordination and an electrophilic pathway rather than a formal C-H activation of the arene followed by alkene hydrometallation, and advocates the necessary cautious approach to labeling this reaction as a C-H functionalization... 

Reetz and Sommer then studied the intramolecular hydroarylation of alkynes when they were looking for carbon triple bond coupling reactions. Depending on the substrate, the choice of gold(I) or gold(III) species was crucial [127]. 

In the presence of BiCU, the hydroarylation of styrenes Ar,C(R)=CH2 with electron-rich arenes ArH afforded Markovnikov adducts Ar C(R)(Ar)Me selectively in good to high yields as a result of the C-H activation of ArH. Under arene-free conditions, the intermolecular hydroarylation of a-substituted styrenes and subsequent intramolecular hydroarylation produced the cyclic dimers of a-substituted styrenes in good yields.122,123... 

Scheme 8. Typical heterocycles from intramolecular hydroarylation.

The palladium-catalyzed hydroboration of allyl phenyl ether 456 is followed by cyclization of the corresponding triflate to afford the chroman core of the tocopheryls 457 (Equation 186) <1998JA9074>. The intramolecular hydroarylation of l-(but-3-enyloxy)-3,5-dimethylbenzene to afford 4,5,7-trimethylchroman can be accomplished using a RuCh/AgOTf catalytic system (Equation 187) <20040L581>. 2,2-Dimethylchromans 458 are formed by a Mo(CO)6 catalyzed intramolecular cyclization of aryl prenyl ethers 459 (Equation 188) <1998S256>. 

The intramolecular hydroarylation of aryl alkynoates to yield 4-substituted coumarins can be catalyzed by palladium(ll) or platinium(iv) (Equation 274) <2000JOC7516, 2003T8859>. The intramolecular hydroarylation of aryl alkynoates can also be carried out in ionic liquids catalyzed by Hf(OTf)4 <2004AGE6183> and under solvent... 

A palladium(ll)-catalyzed intramolecular hydroarylation of a,(3-unstaurated carboxylic acids with electron rich phenols provides straightforward entry to 4-aryldihydrocoumarins 1069 (Equation 419) <2000JOC7516>. 

In the context of the total synthesis of ( )-rhazinilam, an intramolecular hydroarylation of an allene (Scheme 12.23) was investigated.41 The authors report that the Ag(I) complexes were completely ineffective, while AUCI3 delivered 27% of the product and a mixture of 5 mol% AuC13/20 mol% AgOTf gave 82%. The optimum was then reached with 5 mol% Ph3PAuOTf (92% yield). In all cases, the diastereoselectivity was better than 92 8. 

A use of 4A is in the synthesis of 4-substituted tetrahydrocarbazoles and tetrahydro- 3-carbolines, involving cross-metathesis and intramolecular hydroarylation. 

Rhodium(III)-promoted intramolecular hydroarylation or amidoarylation of iV- 3-[(but-3-yn-l-yl)oxy]phenyl acetamides are conditions-controUable to afford chromans or heterocyclic-fiised chromans,respectively (14CC7306). A different rhodium catalyst was applied to the synthesis of ring-fused chromans through decarbonylative alkyne insertion of 2-[(but-3-yn-l-yl)oxy] benzo cyclobutanones (Scheme 29) (14AGE1674). 

Hoffinann HMR, Schmidt B, Wolff S (1989) Preparation of 5-Bromotetronates [4-Alkoxy-5-bromo-2(5/7)-furanones] and a New Concept for the Synthesis of Aflatoxins and Related Structure Types. Tributyltin Hydride versus Palladium-Promoted Intramolecular Hydroarylation. 

The intermolecular hydroarylation of indoles or pyrroles with alkynes in the presence of cationic gold(I) catalysts leads to 2 1-adducts With (Z)-2-en-4-yn-l-ols as an unsaturated reaction partner, indoles are converted into dihydrocyclohepta[ )] indoles in a one-pot reaction sequence that involves a gold-catalyzed intermolecular Friedel-Crafts alkylation followed by an intramolecular hydroarylation (Scheme 4-9). ... 

Gold(lII) chloride and silver hexafluoroantimonate can also be used as catalyst for addition reactions of electron-rich arenes and heteroarenes to olefins. In a similar fashion, the intramolecular hydroarylation of aryl homoallyl ethers and related substrates takes place upon heating with AuCb and AgOTf in dichloroethane to 80 °C and affords dihydrobenzopyrans, tetrahydroquinolines, and tetralins with good yield (Scheme 4-18). ... 

The same catalyst was used by Li and co-workers for an efficient annulation of electron-rich phenols or naphthols with cyelic dienesJ Tricyclic or tetracyclic benzofuran derivatives were obtained as mixtures of syn and anti isomers with the former predominating. The reaetion probably proceeds by intermolecular C-C bond formation via addition of the phenol to the activated diene, followed by protodeauration and intramolecular formation of the C-O bond. In a related transformation, naphthalenes were obtained by treatment of aryl-substituted propargyl esters with eationic gold(I) eatalysts. The reaction may proceed via consecutive 1,3- and 1,2-rearrangements to afford conjugated dienes that then undergo an intramolecular hydroarylation. 

Scheme 7.40 Intramolecular hydroarylation en route to pavine alkaloids.

An asymmetric version of the intramolecular hydroarylation of alkynes (286) to produce fused rings (287) has been developed. With the cationic Pd(II)/(5)-(285) catalyst, the resulting 4-aryl 2-quinolinones were obtained with <98% ee. Asymmetric addition of boronic acids R B(OH)2 to activated cumulenes R C=C=C=C(R )C02Et, catalysed by an NHC-palladium complex, has been shown to yield allenic products R C=C=C(R )CH(R )C02Et with moderate to good enantioselectivities. ... 

Scheme 11.7 illustrates that gold and silver triflate-catalyzed intramolecular hydroarylation of allenic anilines and phenols offers an efficient route to dihydroquinoline and chromene derivatives under mild reaction conditions (Watanabe et al. 2007). The hydroarylation takes place at the terminal or central allenic carbon, depending on the substrate structure, leading to a highly selective formation of six-membered rings. 

Several groups explored the use of [2 + 2 + 2] cycloadditions to form highly functionalized quinazolines. Hua andYang developed a new one-pot synthesis of benzo [/]quinazolines 71, involving a trifluoromethanesulfonic-acid-promoted [2 + 2 + 2] cycloaddition of l,4-diaryl-l,3-butadiynes with nitriles and a subsequent intramolecular hydroarylation (Scheme 33) (13CL769).While the yields were low to moderate, the facility of the reaction and availability of starting materials were noted as some of the advantages of this method. 

A few examples of 2f/-chromenes result from the intramolecular hydroarylation of oxygen-tethered arylalkynyl phenyl sulfides and sulfonamides, catalyzed by FeCl3 and AgOTf. A twofold intramolecular selective 6-endo hydroarylation protocol led to bicyclic products (Scheme 22) (13EJ0533). Under mild conditions, the electrophilic intramolecular twofold iodoarylation of diynyl diethers with iodine monochloride affords high yields of 4,4 -bis(2H-chromenes) (13JOC11382). 

As the intermolecular multicomponent reactions, three-component cycloaddition reactions (21.2 [2+2-1-2] cycloaddition and 21.3 [3+2+1] cycloaddition) and two-component cycloaddition reactions (21.4 [4+2] cycloaddition) are described. As the intramolecnlar single-component reactions, cycloaromatization reactions (21.5 intramolecular hydroarylation of alkynes and cychzation via transition metal vinybdenes) are described. Aromatic ring constrnction reactions involving aryne reactions (Chapter 12), rearrangement reactions (Chapters 16 and 18), metathesis reactions (Chapter 17), and coupling reactions (Chapters 19 and 20) are described in these different chapters. 

In this suhehapter, I summarized the intramoleeular single-component reactions, which are able to construct benzenoid aromatic rings. Two types of cycloaromatization reactions (intramolecular hydroarylation of alkynes and cycUzation via transition metal vinyUdenes) are described. 

The intramolecular hydroarylation of alkynes is a useful method for the synthesis of fused arenes. For example, biphenyl derivatives, bearing an alkyne unit at the ortho position, were converted into substituted phenanthrene derivatives in the presence of various jc-electrophihc transition metal catalysts such as platinum, palladium, gold, gaUium, indium, iron, and so on (Scheme 21.48) [54]. 

SCHEME 21.48 Transition metal-catalyzed intramolecular hydroarylation of alkynes. 

The sequential intramolecular hydroarylation of alkynes is applied to the synthesis of structurally complex extended x-systems. The gold-catalyzed sequential intramolecular hydroarylation of triynes followed by aromatization with DDQ proceeded to give triaryl-substituted diacenaphtho[l,2-y l, 2 -l] fluoranthenes, which can be used for organic light-emitting devices (Scheme 21.49) [55]. 

The sequential intramolecular hydroarylation of alkynes has been applied to the catalytic helicene synthesis. The platinum-catalyzed sequential intramolecular hydroarylation of diynes proceeded to give substituted [6]hehcenes (Scheme 21.50) [56]. 

In this chapter, the intermolecular multicomponent aromatic ring construction reactions and intramolecular single-component aromatic ring construction reactions are described. Among them, the [2+2+2] cycloaddition and intramolecular hydroarylation reactions are the most widely employed and reliable method. Various polycyclic and sterically hindered aromatic compounds have been synthesized by this method. In the past 10 years, the asymmetric [2+2+2] cycloaddition and intramolecular hydroarylation reactions have been developed, which enabled the enantioselec-tive synthesis of sterically hindered chiral aromatic compounds, such as axially chiral biaryls, planar chiral cyclophanes, and helically chiral heUcenes. Details of the transition metal-mediated aromatic ring construction reactions are comprehensively covered in the recently published book... 

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