Tris(pentafluorophenyl)borane‐Assisted Chiral Phosphoric Acid Catalysts for Enantioselective Inverse‐Electron‐Demand Hetero‐Diels‐Alder Reaction of α,β‐Substituted Acroleins

Abstract

In the enantioselective inverse-electron-demand hetero-Diels-Alder reaction, simple α,β-unsaturated aldehydes (i. e., acroleins) are still challenging substrates, unlike α,β-unsaturated carbonyl compounds containing electronwithdrawing groups. In the present study, the reaction of α-aryl-β-alkyl-substituted acroleins with ethyl vinyl sulfide was developed with the use of bulky chiral supramolecular Brønsted acid catalysts, such as tris(pentafluorophenyl) borane-assisted chiral phosphoric acid catalysts. As a result, cis-cycloadducts as optically active 3,4-dihydro-2H-pyrans were exclusively obtained in high yields with high enantioselectivities via the favored endo orbital approach. An obtained optically active cis-isomer could be transformed into the corresponding trans-isomer without a loss of enantiopurity by O,S-acetal epimerization. Moreover, transformations to synthetically useful optically active epoxide and δ-valerolactone are also demonstrated.[a] Dr.

Unusual In‐Situ Preorganization and Postoxidation Steps Observed in Diels‐Alder Reactions of Styrylcyclohexene Dienes

“…The [4+2] cycloadditions of conjugated dienes to various types of multiple bonds, known for nearly one century as the Diels‐Alder (DA) reaction, [1] is perhaps the most practiced method for the construction of six‐membered rings in a single synthetic operation [2] . The ability of the reaction to form up to four stereogenic centers with predictable regiochemistry and absolute configuration, [3] combined with the ease of operation and convenient execution of chiral auxilaries [4] and catalysts [5] have facilitated successful applications of this pericyclic process in stereoselective synthesis of enantioenriched natural products, [6] biologically active compounds, [7] and desired complex molecular structures [8] . Employment of high pressure techniques [9] and Lewis acid mediated methods [10] along with the development of intramolecular, [11] transannular, [12] temporary tethered, [13] self‐assembled, [14] and hetero [15] variants of the reaction have further extended the scope of this remarkable process.…”

Concise and Convergent Enantioselective Total Syntheses of (+)- and (−)-Fumimycin

“…Also, the use of an achiral urea as a cocatalyst, which has been reported to provide both a greater reactivity and a higher selectivity, failed to improve the conversion when used with 12a in our reaction; however, a slightly better enantioselectivity (er 82:18) was detected (Table , entry 7). At this point, we envisioned that the addition of an achiral Lewis acid to form a bulky chiral supramolecular Brønsted acid catalyst, such as the tris­(penta­fluoro­phenyl)­borane-assisted CPA catalyst proposed by Ishihara, would be a highly promising and practical catalyst system to achieve both better conversion and enantioselectivity (Table , entries 8–13). Ultimately, complete conversion accompanied by good enantioselectivity (er 70:30) was achieved using the additive B­(C 6 F 5 ) 3 with 20 mol % loading, a reaction temperature of 85 °C, and a reaction time of 24 h (Table , entry 10) .…”

Enantioselective Povarov Reactions: An Update of a Powerful Catalytic Synthetic Methodology

“…[2,34] In this sense, several smart strategies have been developed to enhance the efficiency of PR, either by lowering the LUMO of the dienes and/or raising the HOMO of the dienophiles, as compiled recently by V. Laina-Martín et al [29] Overall, for the LUMO diene -lowering strategy, chiral acids (such as phosphoric acids) have been employed to interact with the diene usually by establishing hydrogen bond donors. [35,36] For the HOMO dienophile -raising approach, Nitrogenbased compounds (e. g., amines and amino acids) have been chosen as catalysts since they react with aldehydes to form enamines as transient intermediates. These, in turn, are consumed by the diene to produce the desired cycloadduct.…”