Enantioselective Total Synthesis of (−)-Nardoaristolone B via a Gold(I)-Catalyzed Oxidative Cyclization

Abstract

The first enantioselective total synthesis of (−)-nardoaristolone B is accomplished by the implementation of an enantio- and diastereoselective copper(I)-catalyzed conjugate addition/enolate trapping sequence and a gold(I)-catalyzed oxidative cyclization (intermolecular oxidant), employed for the first time in total synthesis.

Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity

“…The gold(I)-catalyzed oxidative cyclization of 1,5-enynes 427 has been recently used as the key step for a concise enantioselective total synthesis of the sesquiterpene (−)-nardoaristolone B ( 504 ) by reaction of dienyne 501 with IPrAuNTf 2 in the presence of 3,5-dichloropyridine N -oxide to form enone 502 , along with the product of cycloisomerization 503 (Scheme 165 ). 446 …”

Asymmetric Sequential Cu‐Catalyzed 1,6/1,4‐Conjugate Additions of Hard Nucleophiles to Cyclic Dienones: Determination of Absolute Configurations and Origins of Enantioselectivity

“…cyclized product P10 was not detected). [26,27] As the tandem 1,4-ACA/enolate trapping appeared difficult to realize, it was decided to perform the cyclization starting from isolated P8, following a procedure already described on similar substrates. [10d,28] In the presence of KH, chloro-ketone P8 was easily converted into P10, which was isolated in a 93% overall yield (d.r.…”

Gold(I)‐Catalysis for the Synthesis of Terpenoids: From Intramolecular Cascades to Intermolecular Cycloadditions

“…Our enantioselective total synthesis of nardoaristolone B ( 122 ) started from 2‐methyl‐2‐cyclohexenone ( 127 ) which was converted into 128 by the enantioselective conjugate addition in the presence of a chiral phosphoramidite ligand and trapping of the resulting enolate with methallyl iodide (Scheme ) . Isomerization of exo ‐olefin of 128 with RhCl 3 ⋅xH 2 O provided ketone 124 .…”

“…Synthetic plan to access (À)-nardoaristolone (122) and (À)-aristolone (123) via the gold(I)-catalyzed oxidative cyclizations of enynes 125 and 126. [132] 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 Our enantioselective total synthesis of nardoaristolone B (122) [139] started from 2-methyl-2-cyclohexenone (127) which was converted into 128 by the enantioselective conjugate addition in the presence of a chiral phosphoramidite ligand and trapping of the resulting enolate with methallyl iodide (Scheme 28). [140] Isomerization of exo-olefin of 128 with RhCl 3 ·xH 2 O provided ketone 124.…”

“…[140] Figure 6. 4,5-seco-Caryophyllane norsesquiterpenoid natural products (137)(138)(139). Scheme 32.…”