A Shimizu Non‐Aldol Approach to the Formal Total Synthesis of Palmerolide A

A formal total synthesis of palmerolide A has been accomplished by assembling three fragments by means of successive Julia–Kocienski olefination, Yamaguchi esterification, and ring‐closing metathesis (RCM). Our initial efforts to combine the first two fragments through a Julia–Kocienski reaction between a secondary sulfone and a ketone were not successful; nevertheless, it was feasible between a primary sulfone and aldehyde. Yamaguchi esterification with the third fragment then set the stage for a RCM reaction. Initial failure of the RCM with a PMB‐ether adjacent to the olefins and the difficulty in cleaving the PMB‐ether prompted us to change the choice of protecting groups, which then paved the way to the macrocyclic core of palmerolide A.     

gem‐Difluoroolefination of Diaryl Ketones and Enolizable Aldehydes with Difluoromethyl 2‐Pyridyl Sulfone: New Insights into the Julia–Kocienski Reaction

The direct conversion of diaryl ketones and enolizable aliphatic aldehydes into gem‐difluoroalkenes has been a long‐standing challenge in organofluorine chemistry. Herein, we report efficient strategies to tackle this problem by using difluoromethyl 2‐pyridyl sulfone as a general gem‐difluoroolefination reagent. The gem‐difluoroolefination of diaryl ketones proceeds by acid‐promoted Smiles rearrangement of the carbinol intermediate; the gem‐difluoroolefination is otherwise difficult to achieve through a conventional Julia–Kocienski olefination protocol under basic conditions due to the retro‐aldol type decomposition of the key intermediate. Efficient gem‐difluoroolefination of aliphatic aldehydes was achieved by the use of an amide base generated in situ (from CsF and tris(trimethylsilyl)amine), which diminishes the undesired enolization of aliphatic aldehydes and provides a powerful synthetic method for chemoselective gem‐difluoroolefination of multi‐carbonyl compounds. Our results provide new insights into the mechanistic understanding of the classical Julia–Kocienski reaction.     

An Efficient Stereoselective Approach for the Synthesis of (+)‐(4S,5S)‐Muricatacin

An efficient stereoselective total synthesis of (+)‐(4S,5S)‐muricatacin was accomplished in good yields from inexpensive, commercially available chemicals ((+)‐diethyl tartrate (DET) and undecan‐1‐ol) by utilizing Mitsunobu and Julia? Kocienski reactions, Wittig homologation, Swern oxidation, and lactonization.     

Stereoselective Total Synthesis of Stagonolide E

An efficient and highly stereoselective synthesis of stagonolide E ( 1 ) starting from the readily available hexane‐1,6‐diol ( 8 ) was accomplished, employing MacMillan α‐hydroxylation, Horner? Wadsworth? Emmons olefination, (Z)‐selective Still? Gennari olefination, and Yamaguchi lactonization as key steps.     

Stereoselective Total Synthesis of Goniothalesdiol A via Chiron Approach

The stereocontrolled synthesis of goniothalesdiol A, a dihydroxylated tetrahydropyran compound, has been accomplished using D ‐ribose as chiral precursor. The key steps involved are aryl Grignard reaction, stereoselective alkoxy‐directed keto reduction, and intramolecular oxy‐Michael addition.     

Stereoselective Total Synthesis of Pectinolides A,C, and H

A simple and straightforward stereoselective total synthesis of Pectinolides A, C, and H is described. The synthesis has been started from commercially available (+)‐diethyl l ‐tartrate and involves Ohira–Bestmann reaction, Corey–Bakshi–Shibata (CBS) reduction, and Still–Gennari olefination as key steps.     

Stereoselective Total Synthesis of Oxylipins: (6S,7E,9R,10S)‐6,9,10‐Trihydroxyoctadec‐7‐enoic Acid and (6Z,8R,9R,10S)‐8,9,10‐Trihydroxyoctadec‐6‐enoic Acid

The stereoselective total syntheses of oxylipins 1b and 1c are described starting from readily accessible natural sugars via the Grubbs cross‐metathesis, Wittig olefination, and Zn‐mediated reductive elimination as key steps.     

Short Enantioselective Total Synthesis of Tatanan A and 3‐epi‐Tatanan A Using Assembly‐Line Synthesis

Short and highly stereoselective total syntheses of the sesquilignan natural product tatanan A and its C3 epimer are described. An assembly‐line synthesis approach, using iterative lithiation–borylation reactions, was applied to install the three contiguous stereocenters with high enantio‐ and diastereoselectivity. One of the stereocenters was installed using a configurationally labile lithiated primary benzyl benzoate, resulting in high levels of substrate‐controlled (undesired) diastereoselectivity. However, reversal of selectivity was achieved by using a novel diastereoselective Matteson homologation. Stereospecific alkynylation of a hindered secondary benzylic boronic ester enabled completion of the synthesis in a total of eight steps.     

The First Stereoselective Total Synthesis of a Naturally Occurring Bioactive Diarylheptanoid, (3R,6E)‐1,7‐Bis(4‐hydroxyphenyl)hept‐6‐en‐3‐ol,through Two Different Approaches

The stereoselective total synthesis of a naturally occurring bioactive diarylheptanoid, (3R,6E)‐1,7‐bis(4‐hydroxyphenyl)hept‐6‐en‐3‐ol, has been accomplished starting from 4‐hydroxybenzaldehyde through two different approaches involving Wittig olefination, hydrolytic kinetic resolution of a racemic epoxide, and olefin cross‐metathesis reaction as the key steps.     

Olefin Cross‐Metathesis: Studies towards the Total Synthesis of (+)‐Bitungolide F

A stereoselective synthesis of (5S,6S)‐6‐[(2S,5S,7R,8E,10E)‐5‐(benzyloxy)‐7‐{[(tert‐butyl)dimethylsilyl]oxy}‐11‐phenylundeca‐8,10‐dien‐2‐yl]‐5‐ethyl‐5,6‐dihydro‐2H‐pyran‐2‐one (=(+)‐9‐O‐benzyl‐11‐O‐[(tert‐butyl)dimethylsilyl]bitungolide F) is reported. The strategy involves Gilman reaction, olefin cross‐metathesis, and Horner? Wadsworth? Emmons olefination as key steps.     

Stereoselective Total Synthesis of 4‐Ketoclonostachydiol

An efficient stereoselective total synthesis of the bioactive 14‐membered natural macrocyclic bislactone 4‐ketoclonostachydiol is described. The strategy involves a Jacobsen's hydrolytic kinetic resolution (HKR), epoxide opening, MacMillan α‐hydroxylation, Horner? Wadsworth? Emmons olefination, a Grignard reaction, and Hoveyda? Grubbs‐II‐catalyzed ring‐closing metathesis (RCM) as key steps.     

Modular Stereoselective Synthesis of (1→2)‐C‐Glycosides based on the sp2–sp3 Suzuki–Miyaura Reaction

This work reports a modular and rapid approach to the stereoselective synthesis of a variety of α‐ and β‐(1→2)‐linked C‐disaccharides. The key step is a Ni‐catalyzed cross‐coupling reaction of D ‐glucal pinacol boronate with alkyl halide glycoside easily prepared from commercially available D ‐glucal. The products of this sp²–sp³ cross‐coupling reaction can be converted to glucopyranosyl, mannopyranosyl, or 2‐deoxy‐glucopyranosyl C‐mannopyranosides by one‐ or two‐step stereoselective oxidative–reductive transformations. To the best of our knowledge, we demonstrated the first synthetic application of a challenging sp²–sp³ Suzuki‐Miyaura cross‐coupling reaction in carbohydrate chemistry.     

Synthesis of (E)‐4‐Bromo‐3‐methoxybut‐3‐en‐2‐one,the Key Fragment in the Polyhydroxylated Chain Common to Oscillariolide and Phormidolides A–C

The terminal bromomethoxydiene (BMD) moiety of the polyhydroxylated chain present in phormidolides and oscillariolides has been synthesized for first time. Several strategies for the stereoselective synthesis of the 4‐bromo‐3‐methoxybut‐3‐en‐2‐ones are described. Furthermore, a preliminary study to successfully introduce the BMD within the polyol chain and the fatty acid allowed us to corroborate the end structure of the polyol.