Asymmetric pyrone Diels–Alder reactions enabled by dienamine catalysis

Abstract

A dienamine mediated asymmetric Diels–Alder reaction between an array of α,β-unsaturated enals and electron-deficient pyrones is presented along with further transformations of the obtained products and models for the observed stereoselectivity.

Asymmetric Synthesis of [2.2.2]-Bicyclic Lactones via All-Carbon Inverse-Electron-Demand Diels–Alder Reaction

“…Notably, the applications of methyl coumalate and related systems in the all-carbon IEDDA reactions with electron-rich double bonds is quite limited and enantioselective variants of such reactions are very limited. 5k , 9 …”

Supramolecular Diversity of Oxabicyclo[2.2.2]octenes Formed between Substituted 2H-Pyran-2-ones and Vinyl-Moiety-Containing Dienophiles

“…For example, in the case of cycloaddition between a substituted 3-acylamino-2H-pyran-2-one and ethyl vinyl ether [17] (or any other suitable alkene dienophile), in the first step a carbon-dioxide bridge system (i.e., 7-oxabicyclo[2.2.2]octene) is formed, such systems (including those formed via other reaction pathways) are known from the literature, but their solid-state structures were described just in a few cases, for some recent examples see ref. [18][19][20][21][22][23][24][25][26][27][28]. However, 7-oxabicyclo[2.2.2]octenes produced as described above can be formed as two possible regioisomers and each of these can exist as a mixture of two diastereoisomers (endo or exo), in turn each of the four distinctive possibilities is actually composed of a pair of enantiomers.…”

“…Symmetry codes for endo-3a: (i) -x + 1, -y + 2, -z + 2; for endo-3b: (i) -x, -y + 1, -z + 1; (ii) x -1, y + 1, z; (iii) -x + 1, -y + 1, -z + 1; for endo-3c: (i) -x + 1, -y, -z; (ii) x +1 2 , -y, -z -1 2 ; for endo-3d: (i) -x, -y + 1, -z, (ii)iv) x, -y + 1, z + 1 2 ; for endo-3e•6a: (i) -x, -y + 1, -z + 2; (ii) -x + 1, -y + 1, -z + 2, (iii) -x + 1, -y + 1, -z + 1; for exo-3e: (i) -x, -y + 2, -z + 1, (ii) -x, -y + 2, -z + 2; for exo-3f:(i) -x + 1, -y + 1, -z + 2, (ii) x + 1, y + 1, z + 1, (iii) -x + 1, -y + 1, -z + 1; for 4a: (i) x, y -1 2 , -z + 3/2, (ii) -x + 1, -y + 2, -z + 2.In compound endo-3b, hydrogen-bonded centrosymmetric tetramer is present, formed via a combination of N1-H29• • • O10 and N2-H30• • • O2 i interactions with the graph-set motif R 4 4(18). In this tetramer, molecule A forms a hydrogen bond through the amide NH group acting as a hydrogen bond donor with the carbonyl oxygen atom of the amide group of molecule B acting as a hydrogen bond acceptor.…”

Asymmetric Inverse-Electron-Demand Diels–Alder Reactions of 2-Pyrones by Lewis Acid Catalysis

“…To date, only a few approaches have been successfully developed. [3][4][5][6][7][8][9][10] Worthy of note, the groups of Deng, 5 Tan 6 and Wang 7 realized the asymmetric normal-electron-demand Diels-Alder (NEDDA) reactions of 3-hydroxyl-2-pyrones with electron-deficient alkenes by hydrogen-bonding organocatalysis (Scheme 2A). In 2014, Beaudary et al utilized this strategy to construct the central distorted phenyl ring with conformational chirality in the enantioselective total synthesis of cyclophane natural product cavicularin (Scheme 1B).…”

“…8 Very recently, Snyder's group achieved asymmetric IEDDA reactions of electron-poor 2-pyrones with 3,3-disubstituted α, βunsaturated aldehydes catalyzed by the chiral secondary amine through dienamine intermediates (Scheme 2B). 9 Among those reported examples, of particularly interest are the enantioselective Diels-Alder reactions of 3-carboalkoxy-2pyrones by Lewis acid catalysis (Scheme 3). 3,4 Upon activation of the diester groups of 2-pyrones by suitable Lewis acids and chiral ligands, these Diels-Alder reactions proceed smoothly in an inverse-electron-demand manner.…”