Pyrrole studies. Part 28. The effect of steric hindrance upon the reaction of 2-vinylpyrroles with dimethyl acetylenedicarboxylate

Abstract

Steric interaction between the N-substituent and the vinyl substituent of 1 -substituted 1 -(1 -substituted pyrrol-2-y1)ethenes destabilises the cisoid conformation (1 b), thereby inhibiting (,4 + =2) cycloaddition reactions leading to dihydroindoles. Bulky N-substituents also sterically inhibit the Michael addition of dimethyl acetylenedicarboxylate at the 5-position of the pyrrole ring.

The Synthesis of η2-β-Vinylpyrrole Complexes and Their Conversion to Highly Substituted Indoles

“…Vinylpyrroles have been extensively studied in the context of polymerization and synthesis of natural products. ,, In particular, vinylpyrroles have been used successfully to prepare indoles via a Diels−Alder cycloaddition with activated alkynes of a suitable preparative method for the 3-vinyl derivatives .…”

“…However, the use of vinylpyrroles in this context has been limited essentially to the 2-vinylpyrroles, owing to the lack, until recently, of a suitable preparative method for the 3-vinyl derivatives . In pioneering studies of Jones et al, 6a-c 2- and 3-vinylpyrroles were observed to react with various alkenes and alkynes to form tetrahydro- and dihydroindoles, respectively. Focusing mainly on 2-vinylpyrroles, these studies demonstrated the potential of such an approach to indoles 41 but also revealed important limitations.…”

“…Many classical organic syntheses of indoles such as the Fischer, Bischler, and Madelung processes fall into this category, as do most organometallic methods of indole synthesis. , Using these methods, functional groups at the 2 and 3 positions are readily installed in the ring-closure sequence; however, the desired substituents at positions 4−7 must be established in the arene precursor. Less common are approaches to indoles that originate with a pyrrole and build up the carbocycle. , As a recent example of the latter approach, several tetrahydroindoles were prepared through a Diels−Alder reaction of a vinylpyrrole and an alkyne dienophile . This methodology offers versatility in the substitution pattern of the carbocycle but suffers from difficulties associated with oxidation of the tetrahydroindole and the tendency of vinylpyrroles to polymerize. 6c, …”

“…Less common are approaches to indoles that originate with a pyrrole and build up the carbocycle. , As a recent example of the latter approach, several tetrahydroindoles were prepared through a Diels−Alder reaction of a vinylpyrrole and an alkyne dienophile . This methodology offers versatility in the substitution pattern of the carbocycle but suffers from difficulties associated with oxidation of the tetrahydroindole and the tendency of vinylpyrroles to polymerize. 6c, …”

Five‐Membered Heterocycles: Pyrrole and Related Systems

“…Other related indole syntheses encompass the use of silyl enol ethers of 2-acylpyrroles [526,527], or a diene generated by S-alkylation of 1-methyl-3-thioacetylpyrrole [528] as the 4p-components. It is also noteworthy that some sterically hindered N-substituted 2-vinylpyrroles give mainly Michael-type addition at C5, as the required cisoid conformation is disrupted by steric interaction between the group at the pyrrole nitrogen and the substituted vinyl moiety [529].…”