5 years ago

α-Sulfinyl Benzoates as Precursors to Li and Mg Carbenoids for the Stereoselective Iterative Homologation of Boronic Esters

α-Sulfinyl Benzoates as Precursors to Li and Mg Carbenoids for the Stereoselective Iterative Homologation of Boronic Esters
Murat Kucukdisli, Giorgia Casoni, Varinder K. Aggarwal, James M. Fordham, Matthew Burns, Eddie L. Myers
The stereoselective reagent-controlled homologation of boronic esters is one of a small number of iteratable synthetic transformations that if automated could form the basis of a veritable molecule-making machine. Recently, α-stannyl triisopropylbenzoates and α-sulfinyl chlorides have emerged as useful building blocks for the iterative homologation of boronic esters. However, α-stannyl benzoates need to be prepared using stoichiometric amounts of the (+)- or (−)-enantiomer of the scarcely available and expensive diamine sparteine; also, these building blocks, together with the byproducts that are generated during homologation, are perceived as being toxic. On the other hand, α-sulfinyl chlorides are difficult to prepare with high levels of enantiopurity and are prone to undergo deleterious acid–base side-reactions under the reaction conditions for homologation, leading to low stereospecificity. Here, we show that the use of a hybrid of these two building blocks, namely, α-sulfinyl triisopropylbenzoates, largely overcomes the above drawbacks. Through either the sulfinylation of α-magnesiated benzoates with either enantiomer of Andersen’s readily available menthol-derived sulfinate or the α-alkylation of enantiopure S-chiral α-sulfinyl benzoates, we have prepared a range of highly enantiopure mono- and disubstituted α-sulfinyl benzoates, some bearing sensitive functional groups. Barbier-type reaction conditions have been developed that allow these building blocks to be converted into lithium (t-BuLi) and magnesium (i-PrMgCl·LiCl) carbenoids in the presence of boronic esters, thus allowing efficient and highly stereospecific homologation. The use of magnesium carbenoids allows carbon chains to be grown with the incorporation of sensitive functional groups, such as alkyl/aryl halides, azides, and esters. The use of lithium carbenoids, which are less sensitive to steric hindrance, allows sterically encumbered carbon–carbon bonds to be forged. We have also shown that these building blocks can be used consecutively in three- and four-step iterative homologation processes, without intervening column chromatography, to give contiguously substituted carbon chains with very high levels of enantio- and diastereoselectivity.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b05457

DOI: 10.1021/jacs.7b05457

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.