Heteroatom-directed intramolecular hydroboration using activated borane complexes

A convenient method for conducting heteroatom-directed intramolecular hydroboration using activated borane complexes was demonstrated. For homoallylic amine boranes, the reaction was initiated by adding iodine, which converts a B-H bond to a reactive B-I leaving group bond. A possible internal S N2-like displacement of the exocyclic iodide leaving group by the tethered olefin then occurs, resulting in a pi complex capable of internal hydroboration. Evidence for an intramolecular reaction includes the high levels of regioselectivity observed for acyclic substrates (up to 43:1), the syn stereochemistry observed for a cyclic amine borane, as well as concentration studies and deuterium labeling experiments that are also consistent with an internal mechanism.; Efforts to expand the scope of the internal hydroboration reaction to allylic amine substrates were not successful. While primary allyl- and crotylamine boranes undergo hydroboration using iodine activation, no decisive evidence for internal hydroboration was found. A preference for C-B bonding closer to nitrogen was found, but the origins of this selectivity remains unclear. Secondary amine boranes undergo facile hydroboration using Ph3C (+) B(ArF)4(-), a reagent initially thought to favor an SN1-like activation pathway, but one that is currently believed to promote N-B bond cleavage and subsequent intermolecular hydroboration.; A study of aminoalkynes revealed that a (bis)homopropargylamine borane is effectively hydroborated using iodine activation. Treatment of the organoborane product with KHF2 provided access to a vinylic potassium trifluoroborate species. This product was coupled to aryl halides using a Suzuki cross-coupling reaction, serving as an application of the hydroboration methodology.; A modified approach to hydroxyl- and ether-directed intramolecular hydroboration was developed since oxygen forms labile complexes with borane. BH3•thioanisole was an effective hydroborating reagent that presumably enables efficient complexation with homoallylic alcohols, alkoxides and ethers. The best levels of regioselectivity were obtained using iodine activation with ether substrates (>14:1), but yields were low due to cleavage of the oxygen protecting group by an SN1- or SN2 mechanism. Switching to TfOH activation was expected to avoid SN2 deprotection, since the counterion, TfO(-) , is non-nucleophilic. Hydroboration using TfOH activation and BH3•thioanisole provided good yields (75%) and high levels of regioselectivity (17:1) for homoallylic ethers containing O-methyl groups.