Naturalproductman’s Blog

Hey, is that a natural product?!

Cascade Heck Reaction

Posted by naturalproductman on July 27, 2009

Yimin Hu et al at Anhui Normal University in China have recently published in Chemical Communications on a Heck-cascade reaction that leads to five contiguous stereocenters.  It’s not only an intermolecular coupling between an aryl halide and an alpha-beta-unsaturated amide, but also a cyclization that leads to the formation of two new rings – it almost looks like a Diels-Alder reaction except that there is an extra functional group introduced.

heck cascade

Chem Comm paper

2 Responses to “Cascade Heck Reaction”

  1. Edinburgher said

    I still remember a sentence of my thesis and a mantra in my former group:

    “Whilst the DA reaction constitute the most powerful tool in the natural product arena to assemble six-membered cyclic systems in a utterly controlled manner, the construction of five and seven-membered carbocycles remains at the forefront of organic reaction development given the…”

    Yep, not a DA but three tertiary and a quaternary centres are set in just one step, in pretty simple conditions. What is the catalyst loading, yields and reaction times?.

    I would bet that the reaction is amenable to be done by using MW, meaning 10-15 min, higher yields an hey presto.medchem guys would love it…

    You dont take holydays, bloody nora!

    Keep the good work

    • naturalproductman said

      Yeah Overman is like the king of the Heck cascade transformations. His research group was also responsible for developing the Aza-Cope-Mannich reaction in applications towards alkaloid total synthesis.

      Going back to this paper: its optimal reaction conditions were 2 mol% Pd(OAc)2 and 4 mol% PPh3, they also have 2 mol equivalents of tributylamine in DMF, and stir for 18 h at 150 degrees C to give 84% yield. They also get the Diels-Alder adduct like by-product (ie: with no aryl group added) at 13%.

      I didn’t know that microwaves are common in industry. I never really looked into those because every lab I was in didn’t have one. I always prefered the old fashion mixing of everything in a flask and stirring in the hood, but I guess times are changing.

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