Annelation reactions

The material in the succeeding chapters describes both the synthesis of the indole ring and means of substituent modification which are especially important in indole chemistry. The first seven chapters describe the preparation of indoles from benzenoid precursors. Chapter 8 describes preparation of indoles from pyrroles by annelation reactions. These syntheses can be categorized by using the concept of bond disconnection to specify the bond(s) formed in the synthesis. The categories are indicated by the number and identity of the bond(s) formed. This classification is given in Scheme 1.1. 

This annelation reaction was also investigated for the 4-bromo-5-ethylthio- and 4-bromo-5-phenylthio-2(5//)-furanones 186 in which the presence of the halogen atom in position 4 of the furanone ring could favor the formation of an-thraquinone derivatives (Scheme 52) (97T1823). Actually, the reaction of the... 

The Robinson annelation reaction has classically been employed for the building up of the six-membered ring components of the steroid nucleus (18). In the original method, the enolate is treated with the methiodide of )9-diethylaminoethyl methyl... 

Hydrogenolysis of methylenediisoxazoles have been useful in preparing substituted resorcinols and aminophenols (7). The isoxazole annelation reaction (71,89,90,91,103) is well suited to the synthesis of steroids and other complex molecules. 

Use of 3-trimethylsilylbut-3-en-2-one in conjugate addition/annelation reaction with 2-methylcyclohexenone after conjugate addition with lithium dimethylcopper. 

Ecologically and economically valuable solvent-free Robinson annelation reactions, which proceed efficiently in a one-pot process at room temperature, have been reported [ 10]. For example, 2-methylcyclohexanone (59), methyl vinyl... 

An enantiospecific, gold-catalyzed pyrrole annelation reaction was utilized in a total synthesis of rhazinilam 95 <06JACS10352>. Specifically, treatment of allene 81 with gold triflate - triphenylphosphine led to the formation of annelated pyrrole 82, which was subsequently converted into 95. A gold-catalyzed direct coupling of pyrroles with 1,3-dicarbonyls led to the formation (3-(pyrrol-2-yl)enones <06ASC331>. 

The electron-rich thiophene ring system can be elaborated into complex, fused thiophenes by acid-mediated intramolecular annelation reactions. For example, treatment of alcohol 96 with trimethylsilyl triflate promoted a Friedel-Crafts acylation and subsequent dehydration giving benzo[b]thiophene 97, a potential analgesic <00JMC765>. Treatment of ketone 98 with p-toluenesulfonic acid resulted in the formation of fused benzo[b]thiophene 99 <00T8153>. Another variant involved the cyclization of epoxide 100 to fused benzo[f>]thiophene 101 mediated by boron trifluoride-etherate . 

An interesting annelation reaction of allene-derived 13-dipoles with 3-(IV-aryliminomethyl)chromones 38 affords, in fair yields, after [4 +3] cycloaddition and a subsequent cascade of rearrangements, derivatives of the novel iV-aryl-2,3-dihydro-4-ethoxycarbonylchromano[2,3-h]azepin-6-one system 39 (for example, R = Me, R1 = Cl) (Scheme 9). In the initial cycloaddition, the substituted chromone acts as an azadiene moiety <00OL2023>... 

Isotetralin, 54, 11 ISOXAZOLE ANNELATION REACTION 1-METHYL-4,4a,5,6,7,8-HEXA-HYDRONAPHTHALEN-2 (3H) -ONE,... 

As dibromocyclopropanes can easily be synthesized by reacting a cycloalkene with bromoform in the presence of a base [16], this method affords an alternative procedure for cyclopentenone annelation onto cyclic alkenes. It should be noted that in the Pauson-Khand reaction, which is probably the most direct cyclopentenone annelation reaction, the reaction using cyclohexene gives the product only in very low yield [11,17]. Also, the position of the original alkynyl substituent on the product double bond is opposite to that in the present reaction. Thus the two reactions are complementary. 

The reactions of fused and unfused a-pyrones with magnesium alkoxides, sodium alkoxides, and water as the nucleophile have been studied in depth, particularly with respect to the effects of chelation <1996J(P1)2715>. The annelation reactions of pyranose derivatives, with acetylacetone and ethyl acetoacetate, to give a variety of annelated fused pyrans have been reported, with the products obtained as single diastereoisomers (Scheme 13) <1997LA1019>. 

Problem 17.49 The Robinson annelation reaction for synthesizing fused rings uses Michael addition followed by intramolecular aldol condensation. Illustrate with cyclohexanone and methyl vinyl ketone, CHj=CHCOCH,. <... 

Annelation Reaction By Using Heterocyclic Compounds T. Kametani and H. Nimoto, Heterocycles, 1978, 10, 349-390. 

WICHTERLE REACTION, Modification of the Robinson annellation reaction in which 1,3dichloro-ci,r-2-butene is used instead of methyl vinyl ketone... 

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