Synthesis of dysideaproline E using organocatalysis

Abstract

(S)-4,4-Dichloro-3-methylbutanoic acid was prepared in 51% overall yield from commercially available starting materials using an organocatalytic transfer hydrogenation to 4,4-dichloro-3-methylbut-2-enal in the key step. The (S)-dichloro acid was used as an intermediate in the first total synthesis of dysideaproline E and a diastereomer confirming the structure of the natural product.

A Ring Closing Metathesis Approach to the Formal Synthesis of (+)‐Callyspongiolide

“…Initially this was achieved by adopting a camphorsultam chiral auxiliary approach (Scheme 6). The chiral auxiliary was removed from alkene 25 , synthesised from (+)‐camphorsultam ( 26 ) according to the procedure of Willis et al [33] . (see SI), and the resulting alcohol protected to give TBS ether 27 .…”

“…Initially this was achieved by adopting a camphorsultam chiral auxiliary approach (Scheme 6). The chiral auxiliary was removed from alkene 25, synthesised from (+)-camphorsultam (26) according to the procedure of Willis et al [33] (see SI), and the resulting alcohol protected to give TBS ether 27. Oxidative cleavage of the olefin in 27 afforded aldehyde 28 which was then subjected to a Horner-Wadsworth-Emmons reaction with phosphonate 29, under Z-selective Ando [34,35] -Touchard [36,37] conditions to afford ester 24 in 79 % yield with a > 19 : 1 Z / E ratio.…”

Advances in the Asymmetric Total Synthesis of Natural Products Using Chiral Secondary Amine Catalyzed Reactions of α,β-Unsaturated Aldehydes

“…In 2011, the Willis group [74] reported the first total synthesis of polychlorinated compound (+)-dysideaproline E (Scheme 26), which had been isolated from marine sponge Dysidea sp. in 2001 by Harrigan group [75].…”

Simple Proline‐Derived Phosphine‐Thiazole Iridium Complexes for Asymmetric Hydrogenation of Trisubstituted Olefins

“…1 H and 13 C NMR signals of this compound are broadened and/or split because of the presence of two slowly interconvertible rotamers. 1 Cbz-l-Proline thioamide (9) [14,15] A mixture of Cbz-l-proline 8 (2.5 g, 10 mmol), Boc 2 O (2.02 g, 10 mmol), (NH 4 ) 2 CO 3 (1.06 g 10 mmol) and pyridine (0.16 mL 2 mmol) in acetonitrile (20 mL) was stirred at room temperature overnight. The acetonitrile was removed and the residue was partitioned in water/EtOAc, then extracted with EtOAc (3 20 mL).…”

“…[14] The amide group of 8 reacted with Lawessons reagent to form the known thioamide 9 in 90 % yield. [15] Compound 9 was cyclized with a-bromoketones in the presence of pyridine in ethanol to produce the thiazole ligands. [16] Although the desired product was obtained in approximately 63 % yield, some racemization occurred when the reaction was performed in ethanol at reflux.…”