Friedel-craft type cyclization

Unusual cyclocarbonylation of allylic acetates proceeds in the presence of acetic anhydride and an amine to afford acetates of phenol derivatives. The cinnamyl acetate derivative 408 undergoes carbonylation and Friedel-Crafts-type cyclization to form the a-naphthyl acetate 410 under severe condi-tions[263,264]. The reaction proceeds at 140-170 under 50-70 atm of CO in the presence of acetic anhydride and Et N. Addition of acetic anhydride is essential for the cyclization. The key step seems to be the Friedel-Crafts-type cyclization of an acylpalladium complex as shown by 409. When MeOH is added instead of acetic anhydride, /3,7-unsaturated esters such as 388 are... 

An interesting intramolecular Friedel-Crafts-type cyclization was developed by Pericas et al. Thus, aryl glycidyl ethers reacted to 3-chromanols as the only reaction product when treated with a catalytic amount of FeBr3 in the presence of AgOTf in CH2CI2 at room temperature (Scheme 9) [26]. The addition of a silver salt proved to... 

Oki and his co-workers (177) also found that these halogenated compounds (107) exhibited enormous differences in reactivity when they were treated with Lewis acids. The sc form undergoes a Friedel-Crafts type cyclization in the presence of titanium tetrachloride, which is a weak Lewis acid, whereas the ap form survives these conditions. The latter reacts in the presence of the stronger Lewis acid antimony pentachloride. This difference is apparently caused by a chloro group in proximity to the site where a cationic center develops during the reaction (Scheme 12). 

The Pictet-Spengler reaction is the method of choice for the preparation of tetrahydro-P-carbolines, which represent structural elements of several natural products such as biologically active alkaloids. It proceeds via a condensation of a carbonyl compound with a tryptamine followed by a Friedel-Crafts-type cyclization. In 2004, Jacobsen et al. reported the first catalytic asymmetric variant [25]. This acyl-Pictet-Spengler reaction involves an N-acyliminium ion as intermediate and is promoted by a chiral thiourea (general Brpnsted acid catalysis). 

As mentioned in the introduction, recent synthetic developments now allow access to the 1,2-thiazine structure via disconnection type C (Figure 23). This process can be accomplished by a Friedel-Crafts-type cyclization of sulfamoyl chlorides. The initial report of this reaction utilized a stoichometric amount of aluminium chloride promoter <19920PP463>. Recently, however, A -ethyl phenethylsulfamoyl chloride 214 was shown to undergo Friedel-Crafts cyclization to form sultam 215 with just a catalytic amount of In(OTf)3 (Equation 33) <2002SL1928>. 

Carbonylation of the 3-phenylallyl acetate 258 under somewhat severe conditions in the presence of tertiary amine and acetic anhydride affords the naphthyl acetate derivative 260. This interesting cyclocarbonylation is explained by the Friedel-Crafts-type cyclization of the acylpalladium 259 as an intermediate [118,119]. Even 5-phenyl-2,4-pentadienyl acetate (261) is cyclocarbonylated to afford 2-phenylphenyl acetate (262) [120],... 

Another effect of the coordination is that the benzylic cation is also stabilized [63]. This stabilization is explained by delocalization of the positive charge due to the interaction of the d-orbital of Cr with the 71-orbital of the benzylic carbon, caused by the coordination of Cr(CO)3. Facile stereospecific Friedel- Crafts-type cyclization of the complex of the optically active benzyl alcohol 248 gave the tetrahydrobenzazepine 249 with retention of the stereochemistry, and the free amine 250 with 98% ee was... 

Servis conditions. The resulting mesylate reacted with excess sodium cyanide in N.N -dimclhylproplcnurea (DPMU) to give the nitrile. The intramolecular Friedel-Crafts type cyclization of the hydrolysis product acid 361 provided... 

Nearly all of the cyclization reactions covered in this section aim at formation of the seven-membered ring. A distinction can be made between acylations at pyrrole rings and Friedel-Crafts type cyclizations at benzene rings. 

A stereoselective Friedel-Crafts type cyclization was used in a strategy to prepare enantioenriched 1,4-dihydro-4-phenylisoquinolines. The products are formed in fair yields and variable ee <03T8049>. Substrates are prepared from (S)-mandelic acid. 

Numerous investigations have centered on the trapping of anodically generated phenoxonium ions with nucleophilic centers tethered to the reacting phenol ring. Much of the early work in this area centered on anodic phenolic coupling reactions, which are essentially Friedel-Crafts type cyclizations, affording spirodienones such as (LIII), often in excellent yield [Eq. (23)] [53]. Anodic cyclizations are treated in detail elsewhere in this edition. 

Sulfones can also be used in Friedel-Crafts-type cyclizations. One example is shown in Scheme 85, where the cyclization in the presence of aluminum chloride of the allylic sulfone occurred in high yield, showing that sulfones can also become electrophiles. Since a tertiary carbanion has about the same stability as a simple allylic cation, tertiary sulfones can also be cyclized (Scheme 85). These last examples illustrated the umpolung provided by the sulfone since carbanion chemistry was used to introduce the 2-methyl groups. 

The dimethylamide function in 27 was reduced by the action of Ti(0/-Pr)4 and phenylsilane [35] to give aldehyde 29, which was then treated with p-TsOH in toluene at room temperature (Scheme 6). Under these reaction conditions, the intramolecular Friedel—Crafts-type cyclization occurred, and the subsequent dehydration of a benzylic alcohol also took place to afford phenanthrofuran skeleton (A-B-C-E ring) 30. The formation of the B-ring by way of intramolecular Friedel—Crafts acylation was first reported by Ginsburg in his synthesis of dihy-drothebainone in 1954 [36]. This transformation was also employed by White in the synthesis of (+)-morphine [37], and by Multzer in the synthesis of dihydrocodei-none [38 -0]. The Friedel—Crafts-type cyclization with an aldehyde function was used by Evans [41] in the formal synthesis of morphine and by Hudlicky in the... 

Scheme 6 Construction of the B-ring by the Friedel—Crafts-type cyclization...

Condensation of arylamine with 1,3-diketone, keto-aldehyde, or dialdehyde, followed by acidic Friedel-Craft type cyclization and dehydration, is well-known as the Combes reaction for quinoline synthesis. 

Scheme 65 Asymmetric Friedel-Crafts-type cyclization in the syntheses of the alkaloids (—)-rhazinal (288), (—)-rhazinilam (289), (—)-leuconolam (290), and (+)-epi-leuconolam (291)...

In the second case the metal acts as a Jt-Lewis acid activating the alkyne for a Friedel-Crafts-type cyclization [90]. With this approach small graphene-type structures can also be efficiently assembled (Scheme 35) [91]. 

Functionalized alkenes containing a phenyl or carboxylic acid group at appropriate distance from the double bond undergo intramolecular cyclization during the sulfonation. On reaction of ( -4-hexenoIc add with SO3 a sulfo 5 lactone is formed (eq 8), and a Friedel-Crafts type cyclization is observed on sulfonation of ( )-5 phenyl-2-pentene (eq 9) both cyclizations proceed quantitatively and stereospedfically. 

Reductive amination of aldehyde-tethered arylnitro derivatives yielded benzazepines in moderate yields (13EJ05262) while the Lewis acid-catalyzed ring contraction-Friedel-Crafts-type cyclization of a series of methoxy-substituted benzothiazines 37 resulted in thiazolo-fused benzazepines 38 (13EJ06291). 

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