Ethyl isocyanoacetate, pyrrole synthesis

The foregoing examples show that the nucleophilic attack to nitroarenes at theorr/io-posidcn followed by cyclizadon is a generid method for the synthesis of various heterocycles. When nucleophiles have an electrophilic center, heterocyclic compounds are obtained in one step. Ono and coworkers have used the anion dedved from ethyl isocyanoacetate as the reacdve anion for the preparadon of heterocyclic compounds. The carbanion reacts with various nitroarenes to give isoindoles or pyriirddines depending on the stnicture of nitroarenes fEqs. 9.56 and9.57. The synthesis of pyrroles is discussed in detail in Chapter 10. 

The Barton-Zard pyrrole synthesis <1990T7587> was applied in the syntheses of pyrrolo[3,4- ]indoles 423 from 3-nitroindoles 422. Treatment of appropriate alkyl 3-nitroindole-l-carboxylates 422a-c with ethyl isocyanoacetate and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave the corresponding pyrrolo[3,4- ]indole 423a-c (Equation 12) <1997CC1873, 1999S1117>. 

Cyclization of 3-nitroindoles 127 with ethyl isocyanoacetate and DBU (conditions of Barton-Zard pyrrole synthesis) gave the corresponding pyrrolo 3,4-fc]indoles 128 (Scheme 22) [35],... 

Pyrrole synthesis. A new route to pyrroles1,2 is based on a base-catalyzed Michael addition of an alkyl isocyanoacetate to a nitroalkene to give an intermediate that cyclizes to a pyrrole. The nitroalkene is generally obtained from a P-acetoxy nitroalkane (1), prepared by a nitro aldol reaction of an aldehyde with a nitroalkane. The synthesis of ethyl 3,4-diethylpyrrole-2-carboxylate (2) is typical. 

Several new examples of the Barton-Zard pyrrole synthesis from nitroalkenes and isocyanoacetate esters demonstrate the broad utility of this procedure. An excellent yield of ethyl 3-(9-anthryl)-4-ethylpyrrole-2-carboxylate was obtained starting with the nitroalkene from anthracene-9-carboxaldehyde and 1-nitropropane. <95TL8457> Bums et.al. reported an improved synthesis of benzyl isocyanoacetate which facilitates the synthesis of benzyl pyrrole-2-carboxylate esters by this method. <95SC379> 3-(l-Arylpyrrol-2-yl)pyrrole-2-carboxylates were prepared from l-aryl-2-(nitrovinyl)pyrroles. <95JHC 1703>... 

Yet another variant which has found some use features /3-nitroacetate precursors <1999JOC6518, 2000J(P1)2977>. An example of this approach has been employed in the preparation of the pyrrole 487 from the nitroacetate 488 during a synthesis of (-F)-deoxypyrrololine (Equation 138) <2001JOC11>. Similarly, pyrroles are also formed upon treatment of /3-sulfonylnitroalkane derivatives with ethyl isocyanoacetate <1997J(P1)3161, 2003TL5163>. 

Gribble and Pelkey adapted the Barton-Zard pyrrole synthesis [84] to 3-nitroindoles and ethyl isocyanoacetate (and tosylmethyl isocyanide) to give 2,4-dihydropyrrolo [3,4-T [indoles (Scheme 15, equation 1) [85, 86], In complementary work, Gribble and cowoikers synthesized pyrrolo[3,4-fc]indoles from the 1,3-dipolar cycloaddition of 2- and 3-nitroindoles with miinchnones (1,3-oxazo-lium-5 elates) (eqnations 2, 3) [87, 88]. The mesoionic miinchnones were generated in situ from the appropriate Af-benzyl-Af-acylamino acids. Gribble and Kishbaugh... 

A mixture of startg. nitroethylene, ethyl isocyanoacetate, and DBU in tetrahydro-furan stirred at room temp, for 15 h ethyl 3-hexyl-4-methylpyrrole-2-carboxylate. Y 78%. F.e.s. N. Ono, K. Maruyama, Bull. Chem. Soc. Japan 61, 4470-2 (1988) review of pyrrole synthesis from aliphatic compds. s. L.N. Sobenina et al., Russ. Chem. Rev. 58, 163-80 (1989). 

Rhodium catalyzed reactions of ethyl isocyanoacetate 353 with 3-fluoroacetylacetone 352 provides a new facile method for the catalytic synthesis of substituted pyrroles. The key step of the reaction is the activation of the C-H bond of isonitrile 353 induced by the a-heteroatom effect. 3-Fluoropyrrole 44 was obtained in 40 % by this method [115]. The mechanism of the transformation includes rhodium promoted decarbonylation of formamide 354 followed by cyclocondensation of intermediate 355 to form the corresponding pyrrole 44. 

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