Synthesis and chemical diversity analysis of bicyclo[3.3.1]non-3-en-2-ones

Jared T. Hammill; Julia Contreras-García; Aaron M. Virshup; David N. Beratan; Weitao Yang; Peter Wipf

doi:10.1016/j.tet.2010.04.112

Synthesis and chemical diversity analysis of bicyclo[3.3.1]non-3-en-2-ones

Jared T. Hammill, Julia Contreras-García, Aaron M. Virshup, David N. Beratan, Weitao Yang, Peter Wipf

Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Functionalized bicyclo[3.3.1]non-3-en-2-ones are obtained from commercially available phenols by a hypervalent iodine oxidation, enone epoxidation, epoxide thiolysis, and intramolecular aldol reaction sequence. Reaction optimization studies identified room temperature as well as microwave-mediated procedures, providing moderate to good yields (57-88%) in the thiophenol-mediated epoxide opening and intramolecular aldol reaction. In addition, the isolation of a key intermediate and in situ NMR studies supported the mechanistic hypothesis. The bicyclic ring products occupy novel chemical space according to ChemGPS and Chemaxon chemical diversity and cheminformatics analyses.

Original language	English
Pages (from-to)	5852-5862
Number of pages	11
Journal	Tetrahedron
Volume	66
Issue number	31
DOIs	https://doi.org/10.1016/j.tet.2010.04.112
State	Published - Jul 31 2010

Bibliographical note

Funding Information:
The authors thank Dr. Steven Geib (University of Pittsburgh) for the X-ray structure analyses of 14 and 20 , and NIH/NIGMS (P41GM081275; P50GM067082) for financial support.

Keywords

Bicyclo[3.3.1]nonenones
Chemical diversity analysis
Epoxyketone rearrangement
Ring-opening

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

Access to Document

10.1016/j.tet.2010.04.112

Cite this

@article{5860a69a7e334f46ae7c23dd17a808ab,

title = "Synthesis and chemical diversity analysis of bicyclo[3.3.1]non-3-en-2-ones",

abstract = "Functionalized bicyclo[3.3.1]non-3-en-2-ones are obtained from commercially available phenols by a hypervalent iodine oxidation, enone epoxidation, epoxide thiolysis, and intramolecular aldol reaction sequence. Reaction optimization studies identified room temperature as well as microwave-mediated procedures, providing moderate to good yields (57-88%) in the thiophenol-mediated epoxide opening and intramolecular aldol reaction. In addition, the isolation of a key intermediate and in situ NMR studies supported the mechanistic hypothesis. The bicyclic ring products occupy novel chemical space according to ChemGPS and Chemaxon chemical diversity and cheminformatics analyses.",

keywords = "Bicyclo[3.3.1]nonenones, Chemical diversity analysis, Epoxyketone rearrangement, Ring-opening",

author = "Hammill, {Jared T.} and Julia Contreras-Garc{\'i}a and Virshup, {Aaron M.} and Beratan, {David N.} and Weitao Yang and Peter Wipf",

note = "Funding Information: The authors thank Dr. Steven Geib (University of Pittsburgh) for the X-ray structure analyses of 14 and 20 , and NIH/NIGMS (P41GM081275; P50GM067082) for financial support. ",

year = "2010",

month = jul,

day = "31",

doi = "10.1016/j.tet.2010.04.112",

language = "English",

volume = "66",

pages = "5852--5862",

number = "31",

}

TY - JOUR

T1 - Synthesis and chemical diversity analysis of bicyclo[3.3.1]non-3-en-2-ones

AU - Hammill, Jared T.

AU - Contreras-García, Julia

AU - Virshup, Aaron M.

AU - Beratan, David N.

AU - Yang, Weitao

AU - Wipf, Peter

N1 - Funding Information: The authors thank Dr. Steven Geib (University of Pittsburgh) for the X-ray structure analyses of 14 and 20 , and NIH/NIGMS (P41GM081275; P50GM067082) for financial support.

PY - 2010/7/31

Y1 - 2010/7/31

N2 - Functionalized bicyclo[3.3.1]non-3-en-2-ones are obtained from commercially available phenols by a hypervalent iodine oxidation, enone epoxidation, epoxide thiolysis, and intramolecular aldol reaction sequence. Reaction optimization studies identified room temperature as well as microwave-mediated procedures, providing moderate to good yields (57-88%) in the thiophenol-mediated epoxide opening and intramolecular aldol reaction. In addition, the isolation of a key intermediate and in situ NMR studies supported the mechanistic hypothesis. The bicyclic ring products occupy novel chemical space according to ChemGPS and Chemaxon chemical diversity and cheminformatics analyses.

AB - Functionalized bicyclo[3.3.1]non-3-en-2-ones are obtained from commercially available phenols by a hypervalent iodine oxidation, enone epoxidation, epoxide thiolysis, and intramolecular aldol reaction sequence. Reaction optimization studies identified room temperature as well as microwave-mediated procedures, providing moderate to good yields (57-88%) in the thiophenol-mediated epoxide opening and intramolecular aldol reaction. In addition, the isolation of a key intermediate and in situ NMR studies supported the mechanistic hypothesis. The bicyclic ring products occupy novel chemical space according to ChemGPS and Chemaxon chemical diversity and cheminformatics analyses.

KW - Bicyclo[3.3.1]nonenones

KW - Chemical diversity analysis

KW - Epoxyketone rearrangement

KW - Ring-opening

UR - http://www.scopus.com/inward/record.url?scp=77955471052&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955471052&partnerID=8YFLogxK

U2 - 10.1016/j.tet.2010.04.112

DO - 10.1016/j.tet.2010.04.112

M3 - Article

AN - SCOPUS:77955471052

SN - 0040-4020

VL - 66

SP - 5852

EP - 5862

JO - Tetrahedron

JF - Tetrahedron

IS - 31

ER -

Synthesis and chemical diversity analysis of bicyclo[3.3.1]non-3-en-2-ones

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this