Directed ortho Metalation-Based Methodology. Halo-, Nitroso-, and Boro-Induced ipso-Desilylation. Link to an in situ Suzuki Reaction

Abstract

[reaction: see text] Treatment of DoM-derived silylated aromatics 2-4 under standard electrophilic halogenation conditions cleanly affords ipso-desilyation products 5-7, while nitration of methoxy-substituted analogues 8, 9 leads to non-ipso isomers 10, 12 and 11, 13, controlled by a silicon steric effect. Sequential ipso-borodesilylation of 2a, 3a, and 20 followed by treatment with aryl halides under Pd-catalyzed conditions constitutes an in situ Suzuki-Miyaura cross-coupling protocol to biaryls and heterobiaryls 23.

Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement

“…After ac onsiderable number of preliminary experiments towards indole 12 entailing C-2 iodination, and subsequent Pd-catalysed coupling reactions, we reverted to as trategy adopted by Snieckusa nd co-workers involving ipso-borodesilylation with boron trichloride, followed by Suzukir eaction of the chloroboranei ntermediate carriedo ut in situ. [23] Thus our targetb uilding block becamet he N-Boc-protected 7bromo-2-trimethylsilylindole (18). This was readily prepared by aB artoli synthesis of 7-bromoindole (16), [24] followed by introductiono ft he Boc-group, and lithiation/silylation of the resulting N-protected indole 17 to give the desired buildingb lock 18 (Scheme 3).…”

“…To this end we investigated two simpler model systems 32 and 35 as substitutes for the real systems 12 and 14,w herein ap henylg roup replacest he tyrosine fragment, not only as model substrates, but also as ac hance to develop and optimize the critical sp 2 -sp 2 coupling methodology.B oth compounds 32 and 35 were synthesized by the initial coupling of either iodobenzene or iodooxazole moiety 25 with the indole derivative 18.T he coupling steps were conducted using the aforementioned ipso-borodesilylation with boron trichloride followed by Suzukireactioncarried out in situ. [23] The optimized Suzuki conditions employed sodium carbonate as base in 1,2-dimethoxyethane (DME) with the reactionc arriedo ut under microwavei rradiation. The Boc protecting group on the indole was removed duringt he coupling, probablyd ue to the formation of hydrochloric acid in the reactionm ixture at the time of the addition of boron trichloride, but this was of little consequence, since it had to be cleaved at some stage.…”

Transition metals in organic synthesis: Highlights for the year 2005

“…Elimination was observed from the sp 3 -bonded iodide [115]. Palladiumcatalyzed couplings of in situ formed aryl dibromoborane with aryl halides [171]. Nitrogen heterocycles can also be used in place of halides and triflates.…”

Directed Metalation–Suzuki–Miyaura Cross-Coupling Strategies: Regioselective Synthesis of Hydroxylated 1-Methyl-phenanthrenes

“…Interestingly, using Br 2 as the electrophile seemed to consistently lead to poor yields in this approach (see also Scheme 2). Therefore, an alternative tactic was adopted and both 1e and 1f were conveniently synthesized by the selective ipso-bromo and -iodo desilylation method 39 of the corresponding silylated derivative 1k (Scheme 2) which was readily available on multigram scale. The requisite boronic acid and bromo derivatives 1i and 1j were obtained by DoM chemistry using the silicon-protection of most reactive metalation site method 35, 36 followed by a second metalation and boronation or 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 bromination.…”