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 language | English (US) |
|---|---|
| Pages (from-to) | 8557-8562 |
| Number of pages | 6 |
| Journal | Journal of Organic Chemistry |
| Volume | 64 |
| Issue number | 23 |
| DOIs | |
| State | Published - Nov 12 1999 |
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ASJC Scopus subject areas
- Organic Chemistry
Cite this
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 journal › Article
}
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.
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U2 - 10.1021/jo990954b
DO - 10.1021/jo990954b
M3 - Article
AN - SCOPUS:0033550305
VL - 64
SP - 8557
EP - 8562
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 23
ER -