A Catalytic, Enantioselective Formal Synthesis of (+)-Dichroanone and (+)-Taiwaniaquinone H

Abstract

A catalytic, enantioselective formal synthesis of (+)-dichroanone and (+)-taiwaniaquinone H is reported. The all-carbon quaternary stereocenter was constructed by asymmetric conjugate addition catalyzed by a palladium(II) (S)-tert-butylpyridinooxazoline complex. The unexpected formation of a [3.2.1] bicyclic intermediate required the identification of a new route. Analysis of the Hammett constants for para-substituted arenes enabled the rational design of a highly enantioselective conjugate addition substrate that led to the completion of the formal synthesis.

Total Synthesis of Cryptotrione

“…We then tried to introduce the isopropyl group stepwise under the conditions developed by Stoltz and coworkers. [16] As expected, bromide 19 smoothly underwent sterically hindered Suzuki-Miyaura coupling with potassium isopropenyltrifluoroborate to produce the alkene 20 in 80 % yield as an inseparable atropisomeric mixture (ca. 3:1).…”

“…Our efforts to direct isopropylation of bromide 19 , using newly developed direct isopropylation conditions, [15] yielded only reductive product 18 and n ‐propyl‐substituted product (see the Supporting Information). We then tried to introduce the isopropyl group stepwise under the conditions developed by Stoltz and co‐workers [16] . As expected, bromide 19 smoothly underwent sterically hindered Suzuki–Miyaura coupling with potassium isopropenyltrifluoroborate to produce the alkene 20 in 80 % yield as an inseparable atropisomeric mixture (ca.…”

Palladium-Catalyzed Asymmetric Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Cyclic Electrophiles

“…31 Here, we recognized that the β-benzylic ketone motif found in conjugate addition products mapped on to the scaffold of taiwaniaquinoid terpene natural products (Scheme 4).…”

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

“…The asymmetric 1,4-addition of arylboronic acids to conjugated cyclic enones and chromones is a very important reaction nowadays. For illustration, the addition products are very promising in medicinal chemistry research [1][2][3][4][5][6][7] and in natural products total syntheses [8][9][10][11][12][13][14][15][16]. Chiral complexes of Rh [17][18][19][20][21][22][23][24] and Pd usually catalyse the reaction, however, palladium holds a special place in this area.…”