A General Synthesis of Pyrroles and Fused Pyrrole Systems from Ketones and Amino Acids

Abstract

The lithium enolates of ketones react with BOC-α-amino aldehydes and BOC-α-amino ketones to afford aldol intermediates that cyclize under acidic conditions to yield pyrroles. The BOC-amino aldehydes and ketones are readily available from α-amino acids. The method allows incorporation of a wide variety of substituents at any of the five atoms of the pyrrole ring and is also suitable for the preparation of fused pyrrole systems.

The Chemistry of α-Haloketones and Their Utility in Heterocyclic Synthesis

“…Effective coupling of organotin(IV) enamines 280 with α-haloketones gave the corresponding 2,4-disubstituted pyrroles 281 at room temperature even under aqueous conditions ( Scheme 82 ) [ 525 , 526 , 527 , 528 , 529 , 530 , 531 , 532 ].…”

Indoles via Dehydrogenation of Pyrroles

“…This method was used in a formal synthesis of chuangxinmycin. As we have seen, a large number of pyrrole → indole dehydrogenations involved the use of a benzoquinone, usu ally DDQ, and a selection of the substrates that were converted to indoles is summarized in Scheme 4 [20][21][22][23][24][25][26][27][28][29]. A new synthesis of N-substituted 7-keto-4,5,6,7-tet rahydroindoles was described by Montalban and coworkers, and these compounds along with the 4-keto analogues were aromatized to the 7-and 4-hydroxyindoles via a halogena tion/dehydrohalogenation protocol (equation 4) [19].…”

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…Thus exposure of 35 to lithium enolates of ketones, followed by cyclization of the resulting aldol adducts 36, produced the set of pyrroles 37 (Scheme 4.12), including several fused derivatives, in low to moderate yields [92]. Reductive cyclization of similar aldol intermediates available from a-(N,N-dibenzyl) amino aldehydes or ketones has been utilized in a related, more high-yielding approach to N-benzylpyrroles [93].…”