Synthesis of Polycyclic Benzofused Nitrogen Heterocycles via a Tandem Benzannulation/Ring-Closing Metathesis Strategy. Application in a Formal Synthesis of (+)-
A two-stage “tandem strategy” for the synthesis of benzofused nitrogen heterocycles is described that is particularly useful for the construction of systems with a high level of substitution on the benzenoid ring. The first stage in the strategy involves a benzannulation based on the reaction of cy...
| Main Authors: | , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Chemical Society
2012
|
| Online Access: | http://hdl.handle.net/1721.1/69574 https://orcid.org/0000-0002-9812-206X |
| _version_ | 1826204026511818752 |
|---|---|
| author | Mak, Xiao Yin Crombie, Aimee L. Danheiser, Rick Lane |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Mak, Xiao Yin Crombie, Aimee L. Danheiser, Rick Lane |
| author_sort | Mak, Xiao Yin |
| collection | MIT |
| description | A two-stage “tandem strategy” for the synthesis of benzofused nitrogen heterocycles is described that is particularly useful for the construction of systems with a high level of substitution on the benzenoid ring. The first stage in the strategy involves a
benzannulation based on the reaction of cyclobutenones with ynamides. This cascade process proceeds via a sequence of four pericyclic reactions and furnishes a multiply substituted aniline derivative which can bear a variety of functionalized substituents at the position ortho to the nitrogen. In the second stage of the tandem strategy, ringclosing metathesis generates the nitrogen heterocyclic ring. This two-step sequence provides efficient access to highly substituted dihydroquinolines, benzazepines, benzazocines, and related benzofused nitrogen heterocyclic systems. The application of this chemistry in a concise formal total synthesis of the anticancer agents (þ)-FR900482 and (þ)-FR66979 is described. |
| first_indexed | 2024-09-23T12:47:40Z |
| format | Article |
| id | mit-1721.1/69574 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:47:40Z |
| publishDate | 2012 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | mit-1721.1/695742022-09-28T10:03:19Z Synthesis of Polycyclic Benzofused Nitrogen Heterocycles via a Tandem Benzannulation/Ring-Closing Metathesis Strategy. Application in a Formal Synthesis of (+)- Mak, Xiao Yin Crombie, Aimee L. Danheiser, Rick Lane Massachusetts Institute of Technology. Department of Chemistry Danheiser, Rick Lane Danheiser, Rick Lane Mak, Xiao Yin Crombie, Aimee L. A two-stage “tandem strategy” for the synthesis of benzofused nitrogen heterocycles is described that is particularly useful for the construction of systems with a high level of substitution on the benzenoid ring. The first stage in the strategy involves a benzannulation based on the reaction of cyclobutenones with ynamides. This cascade process proceeds via a sequence of four pericyclic reactions and furnishes a multiply substituted aniline derivative which can bear a variety of functionalized substituents at the position ortho to the nitrogen. In the second stage of the tandem strategy, ringclosing metathesis generates the nitrogen heterocyclic ring. This two-step sequence provides efficient access to highly substituted dihydroquinolines, benzazepines, benzazocines, and related benzofused nitrogen heterocyclic systems. The application of this chemistry in a concise formal total synthesis of the anticancer agents (þ)-FR900482 and (þ)-FR66979 is described. National Institutes of Health (U.S.) (NIH (GM 28273)) Merck Research Laboratories Boehringer Ingelheim Pharmaceuticals 2012-03-02T19:16:36Z 2012-03-02T19:16:36Z 2011-02 2011-01 Article http://purl.org/eprint/type/JournalArticle 0022-3263 1520-6904 http://hdl.handle.net/1721.1/69574 Mak, Xiao Yin, Aimee L. Crombie, and Rick L. Danheiser. “Synthesis of Polycyclic Benzofused Nitrogen Heterocycles via a Tandem Ynamide Benzannulation/Ring-Closing Metathesis Strategy. Application in a Formal Total Synthesis of (+)-FR900482.” The Journal of Organic Chemistry 76.6 (2011): 1852–1873. https://orcid.org/0000-0002-9812-206X en_US http://dx.doi.org/10.1021/jo2000308 Journal of Organic Chemistry Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society Prof. Danheiser via Erja Kajosalo |
| spellingShingle | Mak, Xiao Yin Crombie, Aimee L. Danheiser, Rick Lane Synthesis of Polycyclic Benzofused Nitrogen Heterocycles via a Tandem Benzannulation/Ring-Closing Metathesis Strategy. Application in a Formal Synthesis of (+)- |
| title | Synthesis of Polycyclic Benzofused Nitrogen Heterocycles via a Tandem Benzannulation/Ring-Closing Metathesis Strategy. Application in a Formal Synthesis of (+)- |
| title_full | Synthesis of Polycyclic Benzofused Nitrogen Heterocycles via a Tandem Benzannulation/Ring-Closing Metathesis Strategy. Application in a Formal Synthesis of (+)- |
| title_fullStr | Synthesis of Polycyclic Benzofused Nitrogen Heterocycles via a Tandem Benzannulation/Ring-Closing Metathesis Strategy. Application in a Formal Synthesis of (+)- |
| title_full_unstemmed | Synthesis of Polycyclic Benzofused Nitrogen Heterocycles via a Tandem Benzannulation/Ring-Closing Metathesis Strategy. Application in a Formal Synthesis of (+)- |
| title_short | Synthesis of Polycyclic Benzofused Nitrogen Heterocycles via a Tandem Benzannulation/Ring-Closing Metathesis Strategy. Application in a Formal Synthesis of (+)- |
| title_sort | synthesis of polycyclic benzofused nitrogen heterocycles via a tandem benzannulation ring closing metathesis strategy application in a formal synthesis of |
| url | http://hdl.handle.net/1721.1/69574 https://orcid.org/0000-0002-9812-206X |
| work_keys_str_mv | AT makxiaoyin synthesisofpolycyclicbenzofusednitrogenheterocyclesviaatandembenzannulationringclosingmetathesisstrategyapplicationinaformalsynthesisof AT crombieaimeel synthesisofpolycyclicbenzofusednitrogenheterocyclesviaatandembenzannulationringclosingmetathesisstrategyapplicationinaformalsynthesisof AT danheiserricklane synthesisofpolycyclicbenzofusednitrogenheterocyclesviaatandembenzannulationringclosingmetathesisstrategyapplicationinaformalsynthesisof |