Tag Archives: anion relay chhemistry

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.

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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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