Cycloalkyne

Source: Wikipedia, the free encyclopedia.

In

transition metals
.

Background

Ring size determines the stability of simple cycloalkynes

Due to the significant geometric constraints imposed by the R−C≡C−R functionality, cycloalkynes smaller than cyclodecyne (C10H16) result in highly strained structures. While the cyclononyne (C9H14) and

natural products and bioorthogonal chemistry.[7][8]

Angle strain

lowest unoccupied molecular orbital, a phenomenon which accounts for the reactivity of strained cycloalkynes from the perspective of molecular orbital theory.[11]

Synthesis

Initial efforts toward the synthesis of strained cycloalkynes showed that cycloalkynes could be generated via the elimination of

allene as the major product.[12]

Further work in this area was aimed at developing milder reaction conditions and generating more robust yields. To circumvent the generation of the undesired

allene, the Kobayashi method for aryne generation was adapted for the synthesis of cycloalkynes.[13]

More recently, a superior method for generating strained cycloalkynes was developed by Fujita. It involves base induced

iodonium salts. The vinyl iodonium proved to be a particularly useful synthetic precursor to strained cycloalkynes due to its high reactivity which arises from the strong electron withdrawing ability of the positively charged iodine species as well as the leaving group ability of the iodonium.[14]

In addition to the elimination-type pathways described, cycloalkynes can also be obtained through the oxidation of cyclic bishydrazones with

lead tetraacetate[3] as well as through the thermal decomposition of selenadiazole.[16]

Reactions

Strained cycloalkynes are able to undergo all addition reactions typical to open chain alkynes. Due to the activated nature of the cyclic carbon–carbon triple bond, many alkyne addition-type reactions such as the Diels–Alder, 1,3-dipolar cycloadditions and

catalysts
frequently required to accelerate the transformation in a non-cyclic system. In addition to alkyne reactivity, cycloalkynes are able to undergo a number of unique, synthetically useful transformations.

Cyclohexyne ring insertion

One particularly intriguing mode of reactivity is the ring insertion of cyclohexyne into cyclic

enone product.[17]

This reaction was utilized as the key step in Carreira's total synthesis of guanacastapenes O and N. It allowed for the expedient construction of the 5-7-6 ring system and provided useful synthetic handles for subsequent functionalization.[18][19]

Copper-free click reaction with cyclooctyne

Cyclooctyne, the smallest isolable cycloalkyne, is able to undergo

bioorthogonal transformation for live cell imaging.[20] Although the mild, copper-catalyzed variant of the reaction, CuAAC (copper-catalyzed azide–alkyne cycloaddition) with linear alkynes had been known, development of the copper-free reaction was significant in that it provided facile reactivity while eliminating the need for a toxic metal catalyst.[21]

References

  1. doi:10.1021/ja00529a057
    .
  2. ^ Cycloalkyne (chemical compound) – Britannica Online Encyclopedia
  3. ^
    ISBN 3-540-11907-8
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  4. doi:10.1021/ja00053a053
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  5. doi:10.1002/cber.19610941213
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  6. doi:10.1002/anie.198912961
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  7. PMID 22422638
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  8. PMID 24724926
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  9. doi:10.1002/ange.19600720914
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  10. doi:10.1016/S0040-4039(01)93113-2
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  11. doi:10.1002/cber.19801130708
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  12. doi:10.1021/ja00884a018
    .
  13. doi:10.1246/cl.1983.1211
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  14. PMID 16104691
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  15. doi:10.1021/ja01134a052
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  16. doi:10.1016/0040-4020(72)80068-1
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  17. doi:10.1002/ange.201001137
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  18. PMID 21370370
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  19. PMID 23080228
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  20. PMID 17942682
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  21. PMID 20309487
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