Pyrroles 1-TIPS-pyrrole

A regiochemical outcome of a palladium-catalyzed direct C-H bond functionalization of the pyrrole ring can be directed by choice of IV-substitution with bulky groups directing to C-3. The oxidative alkenylation of (V-(Boc)pyrrole led selectively to a 2-vinylpyrrole whereas the same reaction with the (V-(TIPS)pyrrole produced a 3-vinylpyrrole <06JACS2528>. 

A more versatile A-protection strategy is seen in Muchowski s A-TIPS-pyrrole (6) [17-19]. Whereas bromination of IV-trimethylsilylpyrrole gives almost exclusively C-2 attack, the NBS bromination of 6 affords the C-3 product 7 in a 96 4 ratio (C-3/C-2) in 93% yield. Deprotection... 

Various iodinated pyiToles have been prepared by direct iodination [19,24] or via thallation [25]. For example, 3-iodo-V-TIPS-pyrrole is prepared in 61% yield from 6 [19], and 3,4-diiodo-2-formyl-l-methylpyrrole is available in 54% yield via a bis-thallation reaction [25]. 

Muchowski has utilized Af-TIPS-3-iodopyrrole to prepare a series of 3-alkynyl pyrroles 119 using standard Sonogashira conditions [59]. Pyrroles 120 were obtained after fluoride cleavage of the TIPS group. Similarly, 3,4-bis(alkynyl)pyrroles were prepared from N-TIPS-3,4-diiodopyrrole [59]. 

Pyrroles are lithiated at the 2-position whether or not the A-protecting group has the ability to coordinate (Scheme 131) . 3-Lithiopyrroles are best obtained by halogen-metal exchange on 3-bromo-A-TIPS pyrrole 275 (Scheme 132). ... 

A crystal structure of a cationic corrin salt has been analyzed.251 The macrocycle is significantly ruffled and the pyrrole ring A is tipped out of the mean plane. The two inner protons are placed on N-21 and N-23. The deviation from the mean plane is small in the metal complexes.252... 

Lithiated pyrroles 101 and 102 readily form from the N-TIPS bromopyrroles, and have been used in the synthesis of analogues of the natural product lyngbyatoxin A.92 Lithiated chloropurine 103 was used in the synthesis of a range of antiviral compounds 93... 

Triple bromination of A -TIPS-pyri ole (6) with NBS affords tribromopyrrole 12 (97%) [22], which can either be deprotected to afford the marine acorn worm metabolite 2,3,4-tribromoindole 13 [22,23] or lithiated selectively at C-2 to give, after quenching with carbon dioxide, pyrrole carboxylic acid 14 [24],... 

Although not a palladium-catalyzed reaction, the Ir(I)-catalyzed C-H borylation reaction developed independently by Smith and Malezcka [58] and Hartwig and Miyaura [59] deserves some mention in the context of indole and pyrrole functionalization. Based on the original studies, indoles and pyrroles can be borylated (and hence cross coupled under Suzuki conditions) to form either the C2 or C3 functionalised products (Scheme 35) [60, 61]. Free (NH)-indoles and pyrroles react exclusively at the C2, whereas /V-TIPS indole and pyrroles are borylated at the C3 positions. Interestingly, Smith, Maleczka and co-workers also demonstrated that when the C2 position of indole is blocked, then the borylation reaction takes place at the C7-position of the indole nucleus [62]. They propose that an A-chelation to Ir (or B) is responsible for the observed selectivity. 

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