Asymmetric Hydroformylation-Initiated Tandem Sequences for Syntheses of (+)-Patulolide C, (−)-Pyrenophorol, (+)-Decarestrictine L, and (+)-Prelog Djerassi Lactone

Abstract

Four different Rh-catalyzed asymmetric hydroformylation (AHF) tandem reactions have been developed in the context of the total syntheses of (+)-patulolide C, (-)-pyrenophorol, (+)-decarestrictine L, and (+)-Prelog-Djerassi lactone. A total synthesis of (+)-patulolide C has been accomplished in three steps utilizing a Rh(I)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of a known alkyne to give a Z-enol acetate with excellent selectivity. An AHF/intramolecular Wittig olefination cascade was utilized to set the C4-hydroxyl stereochemistry, E-olefin geometry, and form the macrolactone. In addition, both (-)-pyrenophorol and (+)-decarestrictine L have been synthesized from the enantiomeric (4R)- and (4S)-4-(tert-butyldimethylsiloxy)-1-pentyne in five and four steps, respectively. These syntheses feature Ru(II)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of terminal alkynes followed by AHF/Wittig olefination sequences to rapidly establish functionality and stereogenicity. A synthesis of (+)-Prelog-Djerassi lactone was accomplished in three isolations from the known 1-vinyl-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane ortho ester. An AHF/crotylation tandem sequence has been developed to set the C2-C4 stereochemistry. An asymmetric hydrogenation was employed to set the C6 stereochemistry, resulting in an especially efficient enantioselective synthesis from achiral starting material. In summary, these syntheses have greatly improved efficiency in terms of atom-economy, catalytic stereoselective transformations, inexpensive reagents, step-counts, and overall yield when compared with previous synthetic attempts.

Carbonylations of Alkenes in the Total Synthesis of Natural Compounds

“…A similar strategy based on the one-pot asymmetric hydroformylation/Wittig reaction was employed in the synthesis of more natural compounds by the same authors. 37 Two asymmetric hydroformylation reactions were utilized in the synthesis of the marine natural compound (+)discodermolide (62) that was developed by Morken and coworkers (Scheme 11). 38 This polyketide, which was isolated in 1990, 39 is a highly complex attractive synthetic subject possessing a considerably promising biological activity.…”

Highly efficient Rh(I)/tris-H8-binaphthyl monophosphite catalysts for hydroformylation of dicyclopentadiene to dialdehydes

“…More importantly, the hydroformylation of olefins yields a mixture of aldehydes which can be further converted to carboxylic acids, alcohols or amines. These products are considered as important versatile intermediates that can be further transformed into a wide variety of high-performance chemicals, such as pharmaceuticals, agro-chemicals, perfumes, and fine chemicals [9][10][11][12][13][14][15]. Dicyclopentadiene (DCPD) is one of the most important components of the C5 fraction in the cracking steam from naphtha and gas oils.…”

Condensation Oligomers with Sequence Control but without Coupling Reagents and Protecting Groups via Asymmetric Hydroformylation and Hydroacyloxylation

“…9 The high level of synthetic versatility accessible at the aldehyde stage makes AHF an attractive disconnection strategy in organic synthesis. Notable recent syntheses of Patulolide C, 10 Garner's aldehyde, 11 the Prelog-Djerassi lactone, 12 the macrolide dictyostatin, 13 γ-chiral α,βunsaturated carbonyl compounds, and vinylogous ester oligomers 14 demonstrate the utility of AHF.…”