Sequential aza-Baylis−Hillman/Ring Closing Metathesis/Aromatization as a Novel Route for the Synthesis of Substituted Pyrroles

Abstract

A new route to diverse 2-substituted-3-methoxycarbonyl pyrroles has been developed. Diverse SES protected alpha-methylene beta-aminoesters were obtained by a 3-component aza-Baylis-Hillman reaction. Diversity arose from the aryl aldehydes which can be used in this reaction. N-Alkylation with allyl bromide under mild conditions provided the corresponding dienes. These substituted dienes were cyclized by ring closing metathesis at room temperature or under microwave-activation with Grubbs-type II catalyst to yield SES-protected pyrroline intermediates. The final pyrroles were obtained by base-promoted dehydrodesulfinylation/aromatization. The scope of each of these reactions was explored.

Ring‐Closing Metathesis: Novel Routes to Aromatic Heterocycles

“…Lamaty and co-workers utilised this strategy in 2004 and developed a new route to 2-substituted 3-methoxycarbonyl pyrroles 70 (Scheme 16). [47] The group employed a three component aza version of the Baylis-Hillman reaction to produce b-aminoesters 67. Treatment of these amines with allyl bromide and a subsequent RCM provided the dihydropyrrole 69 in good yield.…”

Aza‐Baylis–Hillman Reactions and Their Synthetic Applications

“…Scheme 51. Later on, Lamaty et al converted the tosyl group into a SES group by the above methodology. [54] The SES group was then cleaved under basic conditions (Scheme 52).…”

A Metathesis Approach to Aromatic Heterocycles

“…This project was designed to alter the application of the RCM reaction, from one that is capable of forming isolated alkenes to one, which provides intermediates at the correct oxidation state to prepare fully aromatised compounds (in this case heteroaromatic compounds). The use of RCM to form heteroaromatic compounds has only recently appeared in the literature [3][4][5][6][7][8][9][10][11] and given the central position of these compounds to medicinal chemistry another flexible approach was considered to be beneficial. (In some cases the formation of aromatic compounds from a RCM reaction was viewed as an undesirable degradation product following metathesis, see ref.…”