Enantioselective Ir-Catalyzed Hydrogenation of Terminal Homoallyl Sulfones: Total Synthesis of (−)-Curcumene

Abstract

A novel methodology for the preparation of chiral methyl benzylic compounds is reported. Terminal homoallyl sulfones were prepared from homoallyl alcohols, which are easily accessible through the recently reported Lewis acid isomerization of oxetanes. The iridium-catalyzed asymmetric hydrogenation of homoallylic sulfones afforded γ-chiral sulfones with excellent enantioselectivities (up to 98% ee). The synthetic potential of this novel methodology was demonstrated by the total synthesis of (R)-(−)-curcumene.

Regioselective Ring‐Opening of Oxetanes Catalyzed by Lewis Superacid Al(C6F5)3

“…[39] Among this group of compounds, we have recently enantioselectively synthesized (R)-curcumene. [30] Based on a similar strategy, we envisioned the formal synthesis of (R)-curcuquinone in 7 steps (Scheme 4).…”

“…( R ) ‐ Curcuquinone belongs to the bisabolene family of sesquiterpenes which have attested antimicrobial and antifungal properties [39] . Among this group of compounds, we have recently enantioselectively synthesized ( R )‐curcumene [30] . Based on a similar strategy, we envisioned the formal synthesis of ( R )‐curcuquinone in 7 steps (Scheme 4).…”

“…Although, in some cases, the first limitation could be addressed by the derivatization to the corresponding homoallylic sulfones, which provides crystallinity and eases the separation of the isomers, [30] we attempted to solve both drawbacks by improving the reactions conditions. We report herein an improved procedure for the regioselective oxetane ring‐opening using the Lewis superacid Al(C 6 F 5 ) 3 .…”

Regiodivergent sulfonylation of terminal olefins via dearomative rearrangement

“…6 f – k Currently, there are several synthetic approaches to prepare allylsulfones. The traditional approaches are to either use the Tsuji–Trost reaction (Pd 7 or Ir 8 ) 9 for allylsulfones 10 or sulfonyl radical additions to prepare α-sulfonylmethyl styrenes. 11–13 Alternatively, the stoichiometric oxidation 14 of sulfides with strong oxidants has also provided allylsulfones.…”

Catalytic Enantioselective Electrophilic Difunctionalization of Unsaturated Sulfones

“…Thanks to the acidity of the α-hydrogen of sulfone groups, sulfones can serve as important components in Julia olefination and Ramberg–Bäcklund reactions . Due to these advantages, considerable attention has been paid to the synthesis of sulfones, especially those enantioenriched with remote stereogenic centers. − In this regard, methods via the asymmetric radical sulfonylation of terminal alkenes have been developed to access chiral sulfones with a β stereogenic center (Scheme b, upper right) . Besides, approaches via the asymmetric conjugate addition of α,β-unsaturated sulfones and the asymmetric hydrogenation of unsaturated sulfones have been demonstrated to yield chiral sulfones with remote stereogenic centers (Scheme b, bottom). − Despite these advances, the formed chiral sulfones are limited in structure, which restricts their wide applications.…”