A → J Prostaglandin Swap:  A New Tactic for Cyclopentenone Prostaglandin Synthesis

Abstract

A practical methodology for the synthesis of J-type prostaglandins has been developed starting from the well-consolidated approaches established for the synthesis of A-type prostaglandins. An efficient 1,3-allylic transposition of the C-9 hydroxyl group of intermediate 4 furnished the advanced precursor 5 for J(2) synthesis. Our optimized A-J swap protocol employed selenium chemistry, involving the [2,3] sigmatropic rearrangement of secondary allylic selenoxide 11a.

Synthesis of Chiral Cyclopentenones

“…Vidari and co-workers also reported the synthesis of 15-deoxy-Δ 12,14 -PGJ 2 through application of the A−J swap. 573 15-deoxy-Δ 12,14 -PGJ 2 was prepared using Kobayashi's strategy 574 (Scheme 300). This method has also been applied by other authors.…”

“…Further steps including successive hydrolysis, oxidation, and deprotection resulted in target molecule 15-deoxy-Δ 12,14 -PGJ 2 . Vidari and co-workers also reported the synthesis of 15-deoxy-Δ 12,14 -PGJ 2 through application of the A–J swap …”

A Divergent Enantioselective Synthesis of 9‐J1‐Phytoprostane and 9‐A1‐Phytoprostane Methyl Ester

“…The S absolute stereochemistry of the alcohol in the α side‐chain precursor 6 was secured by a regio‐ and stereocontrolled nucleophilic oxirane ring‐opening of ( S )‐glycidyl benzyl ether 8 by hept‐6‐ynoic acid TIPS ester 7 . Sulfone 5 converged to sulfone 4 via cyclopentenyl aryl selenoether intermediate 9 using our swap protocol 8. The ethyl group of the ω side‐chain of 1 and the methyl ester of 2 was obtained from the reduction of tosylhydrazone 10 with (Ph 3 P) 2 CuBH 4 to give the corresponding hydrocarbon 9.…”

“…Subsequently, sulfone 4 , a key building block for the synthesis of phytoprostane 1 and the divergent synthesis of phytoprostane 2 was easily prepared by chemoselective oxidation of 16 with H 2 O 2 in the presence of a catalytic amount of (NH 4 ) 2 MoO 4 in methanol at room temp 12. A divergent route to 2 from sulfone 4 was accomplished after cleavage of the TBDPS group, using our “swap” strategy,8 via 2‐nitrophenyl selenyl ether 9 , which was prepared in 90 % yield using 2‐nitrophenyl selenocyanate in the presence of n Bu 3 P in THF at room temp. Hydrogen peroxide [H 2 O 2 (30 %), pyridine, THF, 7 °C] smoothly triggered the [2,3]‐sigmatropic rearrangement of the corresponding secondary allylic selenoxide 9a to give the desired alcohol (i.e., 5a ) in 60 % isolated yield.…”

Theoretical Studies of [2,3]-Sigmatropic Rearrangements of Allylic Selenoxides and Selenimides

“…[2,3]-Sigmatropic rearrangements of allylic selenoxides and selenimides ( Figure 1 a) are important tools for the synthesis of primary, secondary and tertiary allylic alcohols and amines [ 1 ]. Examples of applications of interest to natural products and bioorganic chemistry include the conversion of A-type prostaglandin to J-type [ 2 ], the enantioselective total synthesis of the marine oxylipin solandelactone E [ 3 ], as well as in the synthesis of sterols [ 4 ] and non-natural amino acids [ 5 ]. [2,3]-Sigmatropic rearrangements of selenoxides have also been used for intrastrand cross-linking of DNA [ 6 ].…”