A synthesis of 3-substituted pyrroles through the halogen-metal exchange reaction of 3-bromo-1-(triisopropylsilyl) pyrrole

In our efforts to develop new, practical entries to several unique classes of indole-containing natural products, we needed to develop a method for achieving selective functionalization of the β-position of pyrrole. While interaction of pyrrole with an electrophilic agent generally leads to introduction of a new group into its α-position,¹ it has been demonstrated recently that protection of the pyrrole ring nitrogen with a phenylsulfonyl group² or the bulky triisopropylsilyl group³ can lead to substitution at the βposition. Thus, while NBS reacts with the N-tert-butyldiphenylsilyl derivative of pyrrole to give a mixture of bromopyrroles,⁴ n-triisopropylsilyl derivative 1 gives predominantly the corresponding 3-bromo derivative 2.³.