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. 2009 Nov;2009(32):5487-5500.
doi: 10.1002/ejoc.200900560. Epub 2009 Oct 8.

Divalent and Multivalent Activation in Phosphate Triesters: A Versatile Method for the Synthesis of Advanced Polyol Synthons

Christopher D Thomas  1 , James P McParland, Paul R Hanson
Affiliations

Divalent and Multivalent Activation in Phosphate Triesters: A Versatile Method for the Synthesis of Advanced Polyol Synthons

Christopher D Thomas et al. European J Org Chem. 2009 Nov.

Abstract

The construction of mono- and bicyclic phosphate trimesters possessing divalent and multivalent activation and their subsequent use in the production of advanced polyol synthons is presented. The method highlights efforts to employ phosphate tethers as removable, functionally active tethers capable of multipositional activation and their subsequent role as leaving groups in selective cleavage reactions. The development of phosphate tethers represents an integrated platform for a new and versatile tether for natural product synthesis and sheds light on new approaches to the facile construction of small molecules.

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Figures

Figure 1
Figure 1
Hydrolysis half-life of trimethyl- and dimethylsodium phosphate.
Figure 2
Figure 2
Monocyclic and bicyclic phosphates.
Figure 3
Figure 3
Seminal report of cuprate addition to allylic phosphates.
Figure 4
Figure 4
Examples of allylic phosphate displacements using cuprates.
Figure 5
Figure 5
Olefin metathesis catalysts.
Figure 6
Figure 6
Corey model for rationalizing stereoselectivity.
Figure 7
Figure 7
Features of P-chiral bicyclo[4.3.1]phosphate 4.
Figure 8
Figure 8
Stability of 4 toward acidic conditions.
Figure 9
Figure 9
Possible hydrolysis products from 4.
Figure 10
Figure 10
13C analysis of basic hydrolysis of 4.
Scheme 1
Scheme 1
Synthesis of monocyclic phosphate 1.
Scheme 2
Scheme 2
Preparation of 1,4-diols via phosphate cleavage.
Scheme 3
Scheme 3
Possible modes for cuprate addition.
Scheme 4
Scheme 4
Cuprate addition/phosphate acid cleavage sequence.
Scheme 5
Scheme 5
Methylation/phosphate cleavage.
Scheme 6
Scheme 6
Unsymmetric monocyclic phosphates.
Scheme 7
Scheme 7
Secondary vs. tertiary allylic phosphate leaving groups.
Scheme 8
Scheme 8
Burke method of desymmetrization.
Scheme 9
Scheme 9
Use of RCM in the construction of the P-chiral, bicy-clo[4.3.1]phosphate (S,S,PR)-4.
Scheme 10
Scheme 10
Regio- and diastereoselective reactivity of 4.
Scheme 11
Scheme 11
Cuprate selectivity on endocyclic olefin of 4.
Scheme 12
Scheme 12
Hydroboration/cuprate/cleavage sequence of 4.
Scheme 13
Scheme 13
Construction of complex differentiated polyol subunits from 4.
Scheme 14
Scheme 14
Five-step protocol from (R,R)-21 to polyol 50.
Scheme 15
Scheme 15
CM/hydrogenation/cuprate sequence.
Scheme 16
Scheme 16
Differentiated polyol subunits accessed from 4.
Scheme 17
Scheme 17
Retrosynthetic analysis of dolabelide C.
Scheme 18
Scheme 18
Phosphate-mediated construction of C1–C11 subunit.
Scheme 19
Scheme 19
Final steps to C1–C14 subunit.
Scheme 20
Scheme 20
Retrosynthetic analysis of the C15–C30 subunit.
Scheme 21
Scheme 21
Phosphate-mediated approach to aldehydes 76a and 76b.
Scheme 22
Scheme 22
Alternative approach to C15–C30 subunit.
Scheme 23
Scheme 23
Final steps to the C15–C30 subunit of dolabelide C.
See this image and copyright information in PMC

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