Allylic sulfones in solid-phase synthesis

Preparation of cyclobutylidenes

Wei Chieh Cheng, Chris Halm, Jerry B. Evarts, Marilyn M. Olmstead, Mark J. Kurth

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Polymer-bound allyl sulfones (cf. 9) were utilized in geminal cycloalkylations with epichlorohydrin to generate a cis- phenylsulfonylcyclobutanol derivative (cf. 11) in one step. In the final step of this solid-phase synthetic sequence, cuprate, organomolybdenum, and organopalladium reagents were screened to obtain an optimal protocol for 'traceless' cleavage of cyclobutylidene products from the resin. Among these, palladium-catalyzed allylic alkylation was the most efficient. In addition, highly regioselective nucleophilic attack at the less hindered terminus of the allyl fragment (i.e., overall S(N)2' sulfinate displacement) was observed. Cyclobutylidene diversification was demonstrated by incorporating different allylic substituents, O-functionalizations, and C-nucleophiles to prepare a demonstration library of eight cyclobutylidene derivatives (i.e., derivatives of 4) in four steps and 30-38% overall yield from lithium polystyrene/divinylbenzene sulfinate.

Original languageEnglish (US)
Pages (from-to)8557-8562
Number of pages6
JournalJournal of Organic Chemistry
Volume64
Issue number23
DOIs
StatePublished - Nov 12 1999

Fingerprint

Sulfones
divinyl benzene
Derivatives
Epichlorohydrin
Nucleophiles
Polystyrenes
Alkylation
Palladium
Lithium
Polymers
Demonstrations
Resins

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Cheng, W. C., Halm, C., Evarts, J. B., Olmstead, M. M., & Kurth, M. J. (1999). Allylic sulfones in solid-phase synthesis: Preparation of cyclobutylidenes. Journal of Organic Chemistry, 64(23), 8557-8562. https://doi.org/10.1021/jo990954b

Allylic sulfones in solid-phase synthesis : Preparation of cyclobutylidenes. / Cheng, Wei Chieh; Halm, Chris; Evarts, Jerry B.; Olmstead, Marilyn M.; Kurth, Mark J.

In: Journal of Organic Chemistry, Vol. 64, No. 23, 12.11.1999, p. 8557-8562.

Research output: Contribution to journalArticle

Cheng, WC, Halm, C, Evarts, JB, Olmstead, MM & Kurth, MJ 1999, 'Allylic sulfones in solid-phase synthesis: Preparation of cyclobutylidenes', Journal of Organic Chemistry, vol. 64, no. 23, pp. 8557-8562. https://doi.org/10.1021/jo990954b
Cheng, Wei Chieh ; Halm, Chris ; Evarts, Jerry B. ; Olmstead, Marilyn M. ; Kurth, Mark J. / Allylic sulfones in solid-phase synthesis : Preparation of cyclobutylidenes. In: Journal of Organic Chemistry. 1999 ; Vol. 64, No. 23. pp. 8557-8562.
@article{0ef3facc4e8845b5bb8b1d1f6c58b1c1,
title = "Allylic sulfones in solid-phase synthesis: Preparation of cyclobutylidenes",
abstract = "Polymer-bound allyl sulfones (cf. 9) were utilized in geminal cycloalkylations with epichlorohydrin to generate a cis- phenylsulfonylcyclobutanol derivative (cf. 11) in one step. In the final step of this solid-phase synthetic sequence, cuprate, organomolybdenum, and organopalladium reagents were screened to obtain an optimal protocol for 'traceless' cleavage of cyclobutylidene products from the resin. Among these, palladium-catalyzed allylic alkylation was the most efficient. In addition, highly regioselective nucleophilic attack at the less hindered terminus of the allyl fragment (i.e., overall S(N)2' sulfinate displacement) was observed. Cyclobutylidene diversification was demonstrated by incorporating different allylic substituents, O-functionalizations, and C-nucleophiles to prepare a demonstration library of eight cyclobutylidene derivatives (i.e., derivatives of 4) in four steps and 30-38{\%} overall yield from lithium polystyrene/divinylbenzene sulfinate.",
author = "Cheng, {Wei Chieh} and Chris Halm and Evarts, {Jerry B.} and Olmstead, {Marilyn M.} and Kurth, {Mark J.}",
year = "1999",
month = "11",
day = "12",
doi = "10.1021/jo990954b",
language = "English (US)",
volume = "64",
pages = "8557--8562",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "23",

}

TY - JOUR

T1 - Allylic sulfones in solid-phase synthesis

T2 - Preparation of cyclobutylidenes

AU - Cheng, Wei Chieh

AU - Halm, Chris

AU - Evarts, Jerry B.

AU - Olmstead, Marilyn M.

AU - Kurth, Mark J.

PY - 1999/11/12

Y1 - 1999/11/12

N2 - Polymer-bound allyl sulfones (cf. 9) were utilized in geminal cycloalkylations with epichlorohydrin to generate a cis- phenylsulfonylcyclobutanol derivative (cf. 11) in one step. In the final step of this solid-phase synthetic sequence, cuprate, organomolybdenum, and organopalladium reagents were screened to obtain an optimal protocol for 'traceless' cleavage of cyclobutylidene products from the resin. Among these, palladium-catalyzed allylic alkylation was the most efficient. In addition, highly regioselective nucleophilic attack at the less hindered terminus of the allyl fragment (i.e., overall S(N)2' sulfinate displacement) was observed. Cyclobutylidene diversification was demonstrated by incorporating different allylic substituents, O-functionalizations, and C-nucleophiles to prepare a demonstration library of eight cyclobutylidene derivatives (i.e., derivatives of 4) in four steps and 30-38% overall yield from lithium polystyrene/divinylbenzene sulfinate.

AB - Polymer-bound allyl sulfones (cf. 9) were utilized in geminal cycloalkylations with epichlorohydrin to generate a cis- phenylsulfonylcyclobutanol derivative (cf. 11) in one step. In the final step of this solid-phase synthetic sequence, cuprate, organomolybdenum, and organopalladium reagents were screened to obtain an optimal protocol for 'traceless' cleavage of cyclobutylidene products from the resin. Among these, palladium-catalyzed allylic alkylation was the most efficient. In addition, highly regioselective nucleophilic attack at the less hindered terminus of the allyl fragment (i.e., overall S(N)2' sulfinate displacement) was observed. Cyclobutylidene diversification was demonstrated by incorporating different allylic substituents, O-functionalizations, and C-nucleophiles to prepare a demonstration library of eight cyclobutylidene derivatives (i.e., derivatives of 4) in four steps and 30-38% overall yield from lithium polystyrene/divinylbenzene sulfinate.

UR - http://www.scopus.com/inward/record.url?scp=0033550305&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033550305&partnerID=8YFLogxK

U2 - 10.1021/jo990954b

DO - 10.1021/jo990954b

M3 - Article

VL - 64

SP - 8557

EP - 8562

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 23

ER -