Publication of the week, number 107, 11th December 2015

I see the Smith lab at University of Pennsylvania is still running relays. In this weeks ASAP they present a new aldehyde linchpin that would enable the construction of propionate-containing natural products exploiting the Type II anion relay chemistry tactic.

Just to remind everyone “In Type II ARC, an external nucleophile is first added to a bifunctional linchpin to generate alkoxide, which upon triggering the Brook rearrangement, either by change in solvent polarity, temperature, and/or counterion, the negative charge is then transferred to a new carbon site. Subsequent trapping with an electrophile furnishes the three-component adduct .”

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So the new linchpin aldehyde is a simple structure easily prepared in 5 steps in 53% overall yield from 2-methylpropane-1,3-diol.

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It can also be prepared from Roche ester giving the chiral synthon in 6 steps.

The aldehyde is readily attacked by a wide variety of nucleophiles and the anion trapped by an equally wide variety of electrophiles. The addition is syn and some interesting products can be synthesised for example:

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The yields are generally high averaging around 70% and the syn:anti ratio is greater than 20:1.

Obviously one application is the use in natural product synthesis. Smith chose the C19-C29 fragment of rhizopodin, a simple little molecule, to demonstrate the versatility of this synthetic method.

What follows is more or less standard approaches to the various component fragments necessary for this approach.

Screen Shot 2015-12-10 at 09.05.20

It results in some nice chemistry and almost gives the natural product fragment. The epoxide seems to be very reluctant to open! Which is a shame as it means looking at alternatives.

The type 1 anion relay also made an appearance this week in JACS. It was involved in the total synthesis of (−)-Enigmazole A.

Useful synthetic methodology here with the potential for scale-up. It would be nice to see others employing these synthons.

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Prof. dangerdackel (199 Posts)


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