Tri-substituted cyclooctene synthesis at the limits of relay ring-closing metathesis: a racemic difluorinated analog of fucose

Ian W. Ashworth, Jonathan A. L. Miles, David J. Nelson, Jonathan M. Percy, Kuldip. Singh

Research output: Contribution to journal › Article

7 Citations (Scopus)

Abstract

A telescoped sequence based on metalated enol acetal chem. allowed the efficient delivery of a ring-closing metathesis (RCM) precursor, which was used to form a cyclooctenone product with a tri-substituted alkenyl group in moderate yield, though a high loading of second generation Grubbs' pre-catalyst was required. A relay RCM precursor was synthesized to deliver the key alkylidene at a higher rate; the catalyst loading required was high, and increasing the reaction temp. simply resulted in the loss of the cyclizing alkylidene by a non-productive cross-metathesis pathway. We were forced to use high diln. conditions to suppress the unwanted CM and secure the cyclooctenone product. The cyclooctenone product could be progressed to analogs of fucose and 6-deoxyidose, e.g. I, by UpJohn dihydroxylation.
LanguageUndefined/Unknown
Pages9637-9646
Number of pages10
JournalTetrahedron
Volume65
Issue number46
DOIs
Publication statusPublished - 2009

Keywords

  • cyclooctene synthesis
  • metathesis
  • fucose

Cite this

Ashworth, Ian W. ; Miles, Jonathan A. L. ; Nelson, David J. ; Percy, Jonathan M. ; Singh, Kuldip. / Tri-substituted cyclooctene synthesis at the limits of relay ring-closing metathesis: a racemic difluorinated analog of fucose. In: Tetrahedron. 2009 ; Vol. 65, No. 46. pp. 9637-9646.
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abstract = "A telescoped sequence based on metalated enol acetal chem. allowed the efficient delivery of a ring-closing metathesis (RCM) precursor, which was used to form a cyclooctenone product with a tri-substituted alkenyl group in moderate yield, though a high loading of second generation Grubbs' pre-catalyst was required. A relay RCM precursor was synthesized to deliver the key alkylidene at a higher rate; the catalyst loading required was high, and increasing the reaction temp. simply resulted in the loss of the cyclizing alkylidene by a non-productive cross-metathesis pathway. We were forced to use high diln. conditions to suppress the unwanted CM and secure the cyclooctenone product. The cyclooctenone product could be progressed to analogs of fucose and 6-deoxyidose, e.g. I, by UpJohn dihydroxylation.",
keywords = "cyclooctene synthesis , metathesis , fucose",
author = "Ashworth, {Ian W.} and Miles, {Jonathan A. L.} and Nelson, {David J.} and Percy, {Jonathan M.} and Kuldip. Singh",
year = "2009",
doi = "10.1016/j.tet.2009.08.076",
language = "Undefined/Unknown",
volume = "65",
pages = "9637--9646",
journal = "Tetrahedron",
issn = "0040-4020",
number = "46",

}

Ashworth, IW, Miles, JAL, Nelson, DJ, Percy, JM & Singh, K 2009, 'Tri-substituted cyclooctene synthesis at the limits of relay ring-closing metathesis: a racemic difluorinated analog of fucose' Tetrahedron, vol. 65, no. 46, pp. 9637-9646. https://doi.org/10.1016/j.tet.2009.08.076

Tri-substituted cyclooctene synthesis at the limits of relay ring-closing metathesis: a racemic difluorinated analog of fucose. / Ashworth, Ian W.; Miles, Jonathan A. L.; Nelson, David J.; Percy, Jonathan M.; Singh, Kuldip.

In: Tetrahedron, Vol. 65, No. 46, 2009, p. 9637-9646.

Research output: Contribution to journal › Article

TY - JOUR

T1 - Tri-substituted cyclooctene synthesis at the limits of relay ring-closing metathesis: a racemic difluorinated analog of fucose

AU - Ashworth, Ian W.

AU - Miles, Jonathan A. L.

AU - Nelson, David J.

AU - Percy, Jonathan M.

AU - Singh, Kuldip.

PY - 2009

Y1 - 2009

N2 - A telescoped sequence based on metalated enol acetal chem. allowed the efficient delivery of a ring-closing metathesis (RCM) precursor, which was used to form a cyclooctenone product with a tri-substituted alkenyl group in moderate yield, though a high loading of second generation Grubbs' pre-catalyst was required. A relay RCM precursor was synthesized to deliver the key alkylidene at a higher rate; the catalyst loading required was high, and increasing the reaction temp. simply resulted in the loss of the cyclizing alkylidene by a non-productive cross-metathesis pathway. We were forced to use high diln. conditions to suppress the unwanted CM and secure the cyclooctenone product. The cyclooctenone product could be progressed to analogs of fucose and 6-deoxyidose, e.g. I, by UpJohn dihydroxylation.

AB - A telescoped sequence based on metalated enol acetal chem. allowed the efficient delivery of a ring-closing metathesis (RCM) precursor, which was used to form a cyclooctenone product with a tri-substituted alkenyl group in moderate yield, though a high loading of second generation Grubbs' pre-catalyst was required. A relay RCM precursor was synthesized to deliver the key alkylidene at a higher rate; the catalyst loading required was high, and increasing the reaction temp. simply resulted in the loss of the cyclizing alkylidene by a non-productive cross-metathesis pathway. We were forced to use high diln. conditions to suppress the unwanted CM and secure the cyclooctenone product. The cyclooctenone product could be progressed to analogs of fucose and 6-deoxyidose, e.g. I, by UpJohn dihydroxylation.

KW - cyclooctene synthesis

KW - metathesis

KW - fucose

U2 - 10.1016/j.tet.2009.08.076

DO - 10.1016/j.tet.2009.08.076

M3 - Article

VL - 65

SP - 9637

EP - 9646

JO - Tetrahedron

T2 - Tetrahedron

JF - Tetrahedron

SN - 0040-4020

IS - 46

ER -

Ashworth IW, Miles JAL, Nelson DJ, Percy JM, Singh K. Tri-substituted cyclooctene synthesis at the limits of relay ring-closing metathesis: a racemic difluorinated analog of fucose. Tetrahedron. 2009;65(46):9637-9646. https://doi.org/10.1016/j.tet.2009.08.076

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