Pyrrolines annulation

The pyrido[3,4- pyridazine 40 was also reacted with l-methyl-2-methylthio-2-pyrroline, at room temperature within 30 min, to give the two isomeric pyrroline-annulated isoquinolines 49 and 50, in an overall yield of 65% with ratio 1 2.3, via elimination of nitrogen and methanethiol from the initially formed cycloadducts <1994H(38)1845>. 

The opening of activated cyclopropanes with nitrogen nucleophiles has been widely applied to the synthesis of pynolizidine and pyrroline alkaloids by Danishefsky this subject has been reviewed. A number of pyrroline annulations have been based on this principle, illustrated in equation (35a). > Similar opening can be accomplished with halides, cuprates, and sulfur or selenium nucleophiles. ... 

Pyrrolines and pyrroles by (4+1) annulation of 2,3-bis(phenylsullony0-1.3-butadlene and amines. 

Pyrrolines and pyrroles can be readily prepared from the rearrangement of a-aminoallenes. Optically enriched a-aminoallene 137 is rearranged to pyrroline 138 by catalytic silver nitrate (Eq. 13.45) [53], The yield of the reaction is high and the cyclization occurs with high levels of asymmetry transfer. Annulated 3-pyrroline 140 is the product of rearrangement of allenyl pyrrolidine 139 (Eq. 13.46) [53]. 

A fundamentally different approach to the synthesis of 3-pyrrolines is evidenced in the annulation in Eq. 13.50 [58]. Ethyl 2,3-butadienoate 150 reacts with N-sulfony-limine 151 in the presence of triphenylphosphine under very mild conditions to give JV-protected 3-pyrroline 152 in 90% yield. The mechanism that has been postulated is related to that of the Baylis-Hillman reaction. Michael addition of triphenylphosphine to the allenyl ester generates a zwitterion that combines with the imine to give 153 in a non-concerted process. This is followed by ring closure, proton exchange and expulsion of triphenylphosphine to give 152. This annulation is successful only for aromatic or cinnamyl imines [59]. 

Similar [3 + 2] annulations of allenylsilanes 86 and propargylsilanes 87 with a, /i-unsaturated ketones, ketones, 7V-acyliminium ions, nitrosonium ions and tropylium cations giving the corresponding cyclopentenes (cyclohexenes), dihydrofurans, 3-pyrrolines, isoxazoles and azulene derivatives, respectively, have been reported (equations 60 and 6i)142.t54,i68-t72>... 

The Sceletium alkaloid ( )-A4 (36) has been synthesized as shown in Scheme 5, using previously developed enamine-vinyl ketone ring annulation methodology (see Vol. 7 of these Reports).12 Treatment of the hydrochloride of the 2-pyrroline (32) with the acetal enone (33) gave a mixture of epimeric keto-acetals (34) in 85%... 

Palladium-catalyzed cyclization of the oxime derivative 47 provided a good yield of the pyrrole 48 (Equation 9) <1999CL45>. Similar reactions have been observed in connection with cyclization studies of related ketone trimethylhydrazonium salts <2005H(65)273>. Photochemical radical cyclization of 7,5-unsaturated ketone oximes has been reported to produce 1-pyrrolines <2005TL2373>. Similar 0-acetyloximes may also be annulated to 1-pyrrolines by treatment with acetic acid in the presence of 1,4-cyclohexadiene and naphthalene-l,5-diol, possibly proceeding via a radical mechanism <2002CL144>. 

Base-induced annulation has also been utilized in a synthesis of, for instance, the fluoroindole 104, which results from a 5-i 6i-/n -cyclization of the precursor 105 (Equation 27). Some related cyclizations could also be used in preparation of fluorinated 2-pyrrolines <2002S1917>. 

Metalation of the amine substrate 184, followed by annulation promoted by tetramethylethylenediamine (TMEDA), gave the intermediate 185, which could thereafter be converted to the fused 3-pyrroline system 186 (Scheme 22). Subsequent dehydrogenation with DDQ gave the corresponding fused pyrrole. This methodology was used for preparation of an extended set of related pyrroles, as well as a series of indole derivatives, which were accessed by lithiation of iV-bromoallyl-2-bromoanilines <2001CEJ2896>. 

Treatment of the aminoketone 243 with lithium trimethylsilyldiazomethane gave the 3-pyrroline 244 (Equation 78). Annulation of related amides provided a corresponding series of 3-pyrroline-2-ones <1996H(42)75>. Likewise, pyrroles may also be obtained upon exposure of N-substituted /3-aminoketones to lithium trimethylsilyldiazomethane <1997SL1063>. 

Taking advantage of an intramolecular Wittig reaction, the a-amidoketones 316 underwent annulation to the 3-pyrrolines 317 upon treatment with the ylide 318 <199581151>. These intermediates could be further elaborated to the pyrroles 319 by base-induced elimination of benzenesulfinic acid (Scheme 37) <2000TL8969>. It should also be mentioned that a set of unusual 3-pyrroline-2-ones have been synthesized by Ugi s four-component reactions from phenacylamine hydrochloride, cyanoacetic acid, cyclohexyl isocyanide, and aldehydes, involving final formation of the C(3)-C(4) bond <1999H(50)463>. 

Likewise, a highly diastereoselective access to trisubstituted 3-pyrrolines by aLkylphosphane-promoted [3+2] annulation of conjugate diene 241 and AT-tosylbenzaldimine 242 was reported by Marinetti and his co-workers, Scheme 3.78 [99],... 

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