Moseley Daniel F, Kalepu Jagadeesh, Willis Michael C
Chemistry Research Laboratory, University of Oxford Mansfield Road Oxford OX1 3TA UK
Chem Sci. 2021 Sep 14;12(39):13068-13073. doi: 10.1039/d1sc03915f. eCollection 2021 Oct 13.
Heterocycle-derived aldehydes are challenging substrates in metal-catalysed hydroacylation chemistry. We show that by using azine N-oxide substituted aldehydes, good reactivity can be achieved, and that they are highly effective substrates for the intermolecular hydroacylation of alkynes. Employing a Rh(i)-catalyst, we achieve a mild and scalable aldehyde C-H activation, that permits the coupling with unactivated terminal alkynes, in good yields and with high regioselectivities (up to >20 : 1 l:b). Both substrates can tolerate a broad variety of functional groups. The reaction can also be applied to diazine aldehydes that contain a free N-lone pair. We demonstrate conversion of the hydroacylation products to the corresponding azine, through a one-pot hydroacylation/deoxygenation sequence. A one-pot hydroacylation/cyclisation, using N-Boc propargylamine, additionally leads to the synthesis of a bidentate pyrrolyl ligand.
在金属催化的氢酰化化学中，杂环衍生的醛是具有挑战性的底物。我们表明，通过使用嗪N-氧化物取代的醛，可以实现良好的反应活性，并且它们是炔烃分子间氢酰化的高效底物。使用Rh(i)催化剂，我们实现了温和且可扩展的醛C-H活化，这允许与未活化的末端炔烃偶联，产率良好且区域选择性高（高达>20:1线性/支化）。两种底物都能耐受多种官能团。该反应也可应用于含有游离N孤对的二嗪醛。我们通过一锅法氢酰化/脱氧序列证明了氢酰化产物向相应嗪的转化。使用N-Boc炔丙胺进行一锅法氢酰化/环化，还可额外合成一种双齿吡咯基配体。
