Sharpless Dihydroxylation Reaction Research Articles

Recent Progress in Chemical Syntheses of Sphingosines and Phytosphingosines

Sphingolipids and their derivatives, such as glycosphingolipids and sphingomyelins, are ubiquitous in the biomembrane of eukaryotic cells, and they play pivotal roles in cell proliferation, recognition, adhesion, and signal transduction. Sphingosine is predominantly the important lipid moiety of the glycosphingolipids and sphingomyelins, while phytosphingosine is a major long-chain moiety for glycosphingolipids. Due to the significance of these two bioactive lipids, tremendous efforts have been made to synthesize sphingosine or phytosphingosine, with chiral pool approaches, chiral auxiliaries, and asymmetric reactions used to construct their contiguous stereogenic centers. This review covers the synthetic literature published from 2000–2015. 1 Introduction 2 Chiral Approach 2.1 Chirality from Sugars 2.2 Chirality from Serine and Its Derivatives 2.3 Chirality from d -ribo-Phytosphingosine 2.4 Chirality from d -Tartaric Acid and Its Diester 2.5 Chirality from Other Chiral Precursors 3 Chiral Auxiliaries 3.1 Chiral Sulfur Auxiliaries 3.2 Chiral N-Containing Auxiliaries 4 Asymmetric Reactions 4.1 Sharpless Dihydroxylation Reaction 4.2 Sharpless Epoxidation and Shi’s Epoxidation Reaction 4.3 Asymmetric Aldol Reaction 4.4 Sharpless Kinetic Resolution 4.5 Asymmetric Aminohydroxylation and Amination 5 Conclusions

ChemInform Abstract: Asymmetric Sharpless Dihydroxylation Reaction of Chiral Bishomoallylic Alcohols: Application to the Synthesis of the C1—C10—C5 Fragment of FR225654.

AbstractA series of different ligands is screened for the asymmetric dihydroxylation of bishomoallylic alcohols to produce 1,2,5‐pentanetriol derivatives.

Asymmetric Sharpless Dihydroxylation Reaction of Chiral Bishomoallylic Alcohols: Application to the Synthesis of the C1–C10–C5 Fragment of FR225654

Toward the synthesis of FR225654, an antidiabetic natural product, the Sharpless asymmetric dihydroxylation of chiral bishomoallylic alcohols, never reported in the literature, was examined. Employing the pyrimidine class of ligands, a high level of matched diastereoselectivity was obtained. An application to the stereoselective synthesis of the C1–C10–C5 fragment of FR225654 was performed.

Total synthesis of the aromatase inhibitor dihydroisocoumarin via protective opening of lactones

Asymmetric total synthesis of a dihydroisocoumarin, (3R,4R)-(−)-6-methoxy-1-oxo-3-pentyl-3,4-dihydro-1H-isochromen-4-yl acetate (1) starting from commercially available m-anisic acid is described. Herein, we depict the use of protective opening of lactones and construction of δ lactone. The synthesis involves Wittig, Grubbs cross metathesis, and Sharpless dihydroxylation reactions.

First stereoselective total synthesis of pectinolide H

The stereoselective total synthesis of bio-active pectinolide H (1) is described. Midland’s asymmetric reduction, Sharpless dihydroxylation reactions are involved in generating the stereogenic centers at C-4′, C-5 and C-1′. Other key steps in the synthesis are Sonogashira cross coupling, Z-selective Still–Gennari olefination, one-pot acetonide deprotection–lactonization, and Lindlar’s reaction. This offers a distinctive strategy for the synthesis of γ-lactones.

Synthesis of chiral alkenyl epoxides: the sex pheromone of the elm spanworm Ennomus subsignaria (Hübner) (Lepidoptera: Geometridae)

The identification of the sex pheromone of the elm spanworm Ennomos subsignaria (Hübner), as the chiral alkenyl epoxide (6Z)- cis-9,10-epoxy-nonadecene has been accomplished. Both enantiomers of (6Z)- cis-9,10-epoxy-nonadecene have been synthesized via two routes. The key steps in the first route were to prepare both threo-epoxy tosylates and then to perform an alkylative rearrangement of these intermediates to obtain the target molecules. An alternative enantioenriched synthesis that took advantage of the Sharpless dihydroxylation reaction was developed so that a common starting material could be used to access both enantiomers. A field study and GC/EAD testing indicated that Z6- cis-9 S,10 R-epoxy-nonadecene was the sex pheromone of the elm spanworm E. subsignaria (Hübner).

Asymmetric synthesis of machilin C and its analogue

AbstractFull details of the asymmetric total synthesis of erythro-8-O-4′-neolignan, machilin C, and its analogue perseal A are reported. The synthesis was involved in the Sharpless dihydroxylation reaction that occurred with excellent asymmetric induction, and the Mitsunobu reaction which occurred with inversion of the absolute configuration from the threo to the erythro isomer. The synthesis was achieved from simple vanillin in eight to twelve steps.

Pteridines. Part CXVII

AbstractA series of side chain reactions starting from the 6‐ and 7‐styryl‐substituted 1,3‐dimethyllumazines 1 and 21 as well as from the 6‐ and 7‐[2‐(methoxycarbonyl)ethenyl]‐substituted 1,3‐dimethyllumazine 2 and 22 were performed first by addition of Br2 to the CC bond forming the 1′,2′‐dibromo derivatives 3, 4, 24, and 26 in high yields (Schemes 1 and 3) (lumazine=pteridine‐2,4(1H,3H)‐dione). Treatment of 3 with various nucleophiles gave rise to an unexpected tele‐substitution in 7‐position and elimination of the Br‐atoms generating 7‐alkoxy‐ (see 5 and 6), 7‐hydroxy‐ (see 7) and 7‐amino‐6‐styryl‐1,3‐dimethyllumazines (see 8–11) (Scheme 1). On the other hand, 4 underwent, with dilute DBU (1,8‐diazabicyclo[5.4.0]undec‐2‐ene), a normal HBr elimination in the side chain leading to 18, whereas treatment with MeONa afforded a more severe structural change to 19. Similarly, 24 and 26 reacted to 27, 32, and 33 under mild conditions, whereas in boiling NaOMe/MeOH, 24 gave 7‐(2‐dimethoxy‐2‐phenylethyl)‐1,3‐dimethyllumazine (30) which was hydrolyzed to give 31 (Scheme 3). From the reactions of 4 and 24 with DBU resulted the dark violet substance 20 and 25, respectively, in which DBU was added to the side chain (Scheme 2). The styryl derivatives 1 and 21 could be converted, by a Sharpless dihydroxylation reaction, into the corresponding stereoisomeric 6‐ and 7‐(1,2‐dihydroxy‐2‐phenylethyl)‐1,3‐dimethyllumazines 34–37 (Scheme 4). The dihydroxy compounds 34 and 35 were also acetylated to 38 and 39 which, on catalytic reduction followed by formylation, yielded the diastereoisomer mixtures 40 and 41. Deacetylation to 42 and 45 allowed the chromatographic separation of the diastereoisomers resulting in the isolation of 43 and 44 as well as 46 and 47, respectively. Introduction of a 6‐ or 7‐ethynyl side chains proceeded well by a Sonogashira reaction with 6‐ (48) or 7‐chloro‐1,3‐dimethyllumazine (55) yielding 49–51 and 56–58 (Scheme 5). The direction of H2O addition to the triple bond is depending on the substituents since the 6‐ (49) and 7‐(phenylethynyl)‐1,3‐dimethyllumazine (56) showed attack at the 2′‐position yielding 53 and 60, in contrast to the 6‐ (51) and 7‐ethynyl‐1,3‐dimethyllumazine (58) favoring attack at C(1′) and formation of 6‐ (52) and 7‐acetyl‐1,3‐dimethyllumazine (59).

An Enantioselective Synthesis of Phomopsolide D.

Abstract A short enantioselective route to the highly functionalized α,β-unsaturated δ-lactone natural product phomopsolide D and three of its stereoisomers, has been accomplished. All of the carbon atoms of phomopsolide D come from tiglic acid and 2-furyl-1-penta-1′,3′-dienylketone (furan plus hexadienal). This approach derives its asymmetry from the sequential use of two catalytic asymmetric reactions; these being a Sharpless dihydroxylation reaction and a Noyori furylketone reduction. The resulting furfuryl alcohols were stereoselectively transformed into α,β-unsaturated δ-lactones via a short highly diastereoselective oxidation and reduction sequence.

An enantioselective synthesis of phomopsolide D

A short enantioselective route to the highly functionalized α,β-unsaturated δ-lactone natural product phomopsolide D and three of its stereoisomers, has been accomplished. All of the carbon atoms of phomopsolide D come from tiglic acid and 2-furyl-1-penta-1′,3′-dienylketone (furan plus hexadienal). This approach derives its asymmetry from the sequential use of two catalytic asymmetric reactions; these being a Sharpless dihydroxylation reaction and a Noyori furylketone reduction. The resulting furfuryl alcohols were stereoselectively transformed into α,β-unsaturated δ-lactones via a short highly diastereoselective oxidation and reduction sequence.