Cyclization allylic derivatives

Bromination of the diphenyl indole derivative 316 with bromine in DMF or trimethylammonium bromide afforded the 7-bromo derivative 317. Reaction with allyl bromide or its derivatives gave A-allyl derivatives 318 that upon cyclization with palladium acetate gave 7,9-dimethoxy-l,2-diphenylpyrrolo[3,2,l-// ]quinoline derivatives 319 (92T7601) (Scheme 57). 

Dialkylindolines and 1,3-dialkylindoles are formed in poor yield (<10%) from the reaction of ethyl- or phenymagnesium bromide with 2-chloro-N-methyl-N-allylaniline in the presence of catalytic quantities of (bistriphenylphosphine)nickel dichloride.72 In a modification of this procedure, the allyl derivatives can be converted by stoichiometric amounts of tetrakis(triphenylphosphine)nickel into 1,3-dialkylindoles in moderate yield72 (Scheme 43) an initial process of oxidative addition and ensuing cyclization of arylnickel intermediates is thought to occur. In contrast to the nickel system,72 it has proved possible to achieve the indole synthesis by means of catalytic quantities of palladium acetate.73 It is preferable to use... 

Morpholinone 177, derived from allyl glycine, cyclized stereoselectively under UV irradiation (A > 342 nm) in the presence of 9,10-anthracene dicarbonitrile (ADC) and biphenyl (PB) to give compound 176 as a single diastereo-isomer <2001JOC6896> (Scheme 26). 

Aryl diazonium ions are converted to iodides in high yield by reaction with iodide salts. This reaction is initiated by reduction of the diazonium ion by iodide. The aryl radical then abstracts iodine from either I2 or I3. A chain mechanism then proceeds which consumes I- and ArN2+.105 Evidence for the involvement of radicals includes the isolation of cyclized products from o-allyl derivatives. 

Imidazo[l,5-a][l,3,5]triazinones (191) have been prepared from pyrimidines such as (190) by cleavage of the C(4)-C(5) bond and cyclization to the desired product (Scheme 116) (79JOC1740). The allyl derivative (192) is formed in the same way (equation 112) (81JOC3681). 

The molybdenum complex [(CF3)2MeCO]2Mo(NAr)(=CHCMe2Ph) has been observed to be a more efficient catalyst for cyclization of vinyl silyl ether dienes than the ruthenium complex Cl2(PCy3)2Ru(=CHPh), probably because this type of alkene is sterically more demanding (than allyl derivatives) and therefore requires a catalyst less sensitive to steric bulkiness near the reaction center. However, some examples of the RCM of substituted vinylsilanes catalyzed by ruthenium complexes have been reported [127, 131] (Eq. 74). For more examples see Ref. [127]. 

Vinylthiopyridines, e.g. (496) and (497), available by various methods, on acid catalysis can be cyclized to dihydrothiazoles. For allyl derivatives (498) cyclization by acid or electrophilic catalysis yields 3-methyl derivatives (81H(15)1349). 

A one-pot procedure for the palladium-catalyzed allylation/cyclization of o-alkynyltrifluoroacetanilides 57a [57] and o-alkynylphenols 57b [58] was developed by Cacchi et al. (Scheme 20). This method provides a valuable tool for the synthesis of 2-substituted-3-allylindoles 58a and 2-substituted-3-allylbenzofurans 58b. It was reported that reaction proceeded through the formation of X-allyl derivatives, which form 7r-allylpalladium species 59. A subsequent rearrangement of 59 would then lead to the 7r-allylpalladium species 60. Intramolecular nucleophilic attack of the hetero atom across the activated carbon-carbon triple bond in 60, followed by reductive elimination of Pd(0) gives the products 58. A similar reaction was reported by Balme et al. [59]. 

Allyl-palladium complexes of pyridine derivatives cyclize to yield pyridinium compounds <03JOM313>. 

Aryl radicals participate in radical cyclization reactions when the aromatic ring has an alkene or alkyne substituent. o-Iodo aryl allyl ethers cyclize to benzofuran derivatives, for example, when treated with AIBN, aqueous H3PO2 and NaHCOs in ethanol. Cyclization of an o-bromo-A-acyl aniline (a methacrylic acid derivative) with AIBN/BusSnH gave an indolone under the typical conditions used for cyclization of alkenes. 

Stork s intramolecular allylic epoxide cyclizations proceed stereospecifically to give cyclo-hehaxonol derivatives <90JAi66i>. The reason for the observed stereospecificity (OH, C02Me cis) can be traced to the energetically more favorable transition-state conformation. This methodology has been applied to enantioselective total syntheses of (— )-histrionicotoxins (Scheme 28) <90JA5875>. 

However, attempts to effect a similar cyclization of [xlvi] and [xlvh] appeared to result in an 8-substituted product [19-20], and Grewe concluded that only hydrocarbon residues can be introduced at C-13 in this way. This was subsequently found to be untrue. Cyclization of the allyl-derivative [xLvm] gave 13-allyloctahydrophenanthrene [xlix, R = CH2 CH=CH2], which was converted to the corresponding aldehyde [xlix, R = CH2 CHO] by ozonolysis [20]. 

The Reformatsky reaction between 2-allylcycZohexanone and ethyl a-bromo-/3-phenylpropionate yielded the acid [l], which on cyclization gave two acids, one of which was the expected 13-allyl-derivative [li]. The other acid did not react with bromine and was allotted the structure [l 11 ] on Curtius degradation it afforded the amine [liii]. The acid [in] was recovered mainly unchanged after heating with spongy palladium at 310° C. for one hour [21]. 

In the case of (bromomcthyl)dimethylsilyl allyl ethers, cyclization of 4-substituted derivatives gives l,5-/rw .f-disubstituted products in accord with the theoretical prediction1. Treatment of the ethers with tributyltin hydride in a free-radical process, followed by successive oxidation with hydrogen peroxide, gives the corresponding 1.3-diols with high stereoselectivity30. The stereoselectivity improves if the bulk of the C-4 substituent is increased. 

With a variant of this procedure it is possible to prepare benz[6]azepines by the acid treatment of o-allyl methylsulfinylacetanilides (174 R = Me or Ts) <90CPB3331>. When stands for methyl or phenyl and R for hydrogen, the products of the cyclization are the 1-endo products, benz[f>]azepines. If, however, this substitution pattern is reversed, quinolines are isolated from (>-exo cyclization. The unsubstituted allyl derivatives fail to cyclize, which is attributed to the reduced nucleophilicity of the alkenyl group. 

The same reaction occurs much more rapidly and without gas evolution with alkylcobalt tetracarbonyls and conjugated dienes (14). Thus, the reaction probably involves the addition of an acylcobalt tricarbonyl to the diene, perhaps by way of a w complex, either 1 2 or 1 4 and then a cyclization to the TT-allyl derivative. 

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