Publication Date:
2016-04-19
Description:
In the classic Diels-Alder [4 + 2] cycloaddition reaction, the overall degree of unsaturation (or oxidation state) of the 4pi (diene) and 2pi (dienophile) pairs of reactants dictates the oxidation state of the newly formed six-membered carbocycle. For example, in the classic Diels-Alder reaction, butadiene and ethylene combine to produce cyclohexene. More recent developments include variants in which the number of hydrogen atoms in the reactant pair and in the resulting product is reduced by, for example, four in the tetradehydro-Diels-Alder (TDDA) and by six in the hexadehydro-Diels-Alder (HDDA) reactions. Any oxidation state higher than tetradehydro (that is, lacking more than four hydrogens) leads to the production of a reactive intermediate that is more highly oxidized than benzene. This increases the power of the overall process substantially, because trapping of the reactive intermediate can be used to increase the structural complexity of the final product in a controllable and versatile manner. Here we report an unprecedented overall 4pi + 2pi cycloaddition reaction that generates a different, highly reactive intermediate known as an alpha,3-dehydrotoluene. This species is in the same oxidation state as a benzyne. Like benzynes, alpha,3-dehydrotoluenes can be captured by various trapping agents to produce structurally diverse products that are complementary to those arising from the HDDA process. We call this new cycloisomerization process a pentadehydro-Diels-Alder (PDDA) reaction-a nomenclature chosen for chemical taxonomic reasons rather than mechanistic ones. In addition to alkynes, nitriles (RC identical withN), although non-participants in aza-HDDA reactions, readily function as the 2pi component in PDDA cyclizations to produce, via trapping of the alpha,3-(5-aza)dehydrotoluene intermediates, pyridine-containing products.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877333/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877333/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wang, Teng -- Naredla, Rajasekhar Reddy -- Thompson, Severin K -- Hoye, Thomas R -- CA76497/CA/NCI NIH HHS/ -- GM65597/GM/NIGMS NIH HHS/ -- R01 CA076497/CA/NCI NIH HHS/ -- R01 GM065597/GM/NIGMS NIH HHS/ -- S10 OD011952/OD/NIH HHS/ -- S10OD011952/OD/NIH HHS/ -- England -- Nature. 2016 Apr 28;532(7600):484-8. doi: 10.1038/nature17429. Epub 2016 Apr 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Minnesota, 207 Pleasant Street, SE, Minneapolis, Minnesota 55455, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27088605" target="_blank"〉PubMed〈/a〉
Keywords:
Benzene/chemistry
;
Cyclization
;
*Cycloaddition Reaction
;
Diynes/chemistry
;
Hydrogen/*chemistry
;
Hydrogenation
;
Isomerism
;
Nitriles/chemistry
;
Oxidation-Reduction
;
Pyridines/chemistry
;
Terminology as Topic
;
Toluene/*analogs & derivatives/chemical synthesis/chemistry
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
