Enantioselective Total Synthesis of (+)-Psiguadial B

Abstract

The first enantioselective total synthesis of the cytotoxic natural product (+)-psiguadial B is reported. Key features of the synthesis include (1) the enantioselective preparation of a key cyclobutane intermediate by a tandem Wolff rearrangement/asymmetric ketene addition, (2) a directed C(sp 3 )−H alkenylation reaction to strategically forge the C1−C2 bond, and (3) a ring-closing metathesis to build the bridging bicyclo[4.3.1]decane terpene framework.

Palladium-Catalyzed Transformations of Alkyl C–H Bonds

“…140–146 In the synthesis of celogentin C ( 136 ), Chen utilized this approach to couple 6-iodo-1-tosyl-1 H -indole with the β-methylene C(sp 3 )–H bond of a valine-derived substrate to give 135 in 80% yield (Scheme 31). 140 In 2012, Baran and coworkers reported the total synthesis of piperaborenine B ( 141 ) using sequential, diastereoselective arylation reactions of cyclobutyl C(sp 3 )–H bonds as the key steps (Scheme 32).…”

“…145 Very recently, Reisman and co-workers accomplished the first enantioselective total synthesis of (+)-psiguadial B. 146 The directed C(sp 3 )–H alkenylation of a chiral cyclobutane 142 could provide the key intermediate 143 in 72% yield on a gram scale (Scheme 33). …”

Convenient Access to Chiral Cyclobutanes with Three Contiguous Stereocenters from Verbenone by Directed C(sp3)−H arylation

“…Here, the cyclobutane scaffold has constituted a particular popular arena for showcasing the utility of this C−H functionalization approach . This has most elegantly been demonstrated by the groups of Baran, and Reismann,– who have employed different 8‐AQ‐directed C−H functionalization reactions in the key steps of total syntheses of different complex natural products (Figure ).…”

Synthesis and antimicrobial evaluation of novel analogues of dehydroabietic acid prepared by C H-Activation

“…The combination of strongly coordinating, bidentate directing groups with late transition metals led to the introduction of a variety of substituents on usually chemically inert C(sp 2 )-and C(sp 3 )-carbons. Although the number of practical applications of such reactions to the total synthesis of natural products or the M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT synthesis of novel analogues is still scarce, additional reports continue to appear [9][10][11]. (4) [12], amination (5) [13] and borylation delivering alcohol (6) [14] on C-19 have been carried out, hinting at the potential of such transformations in medicinal chemistry ( Figure 3).…”