An Efficient Procedure for Palladium-Catalyzed Reduction of Aryl/Enol Triflates

Kotsuki, Hiyoshizo; Datta, Probal K.; Hayakawa, Hisao; Suenaga, Hitoshi

doi:10.1055/s-1995-4120

Cited by 61 publications

(35 citation statements)

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“…We therefore adopted a new synthetic strategy (conversion of the hydroxylated products) to obtain 7b (Chart 2). This approach first converted the pyrazinone 8b into the corresponding triflate 9b, which were then successfully reduced via the triethylsilane-Pd(dppf) 2 Cl 2 system, [14][15][16][17] providing a satisfactory yield of 7b (Chart 2). Fortunately, 2-naphthyl derivative 1b provided single crystals suitable for X-ray crystallographic analysis.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Aldose Reductase Inhibitory Activity of Botryllazine A Derivatives

Saito

Ishibashi

Noumi

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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Aldose reductase (AR) is associated with the onset of diabetic complications. Botryllazine A and its analogues were synthesized and evaluated for human AR inhibitory activity. Analogues possessing aromatic bicyclic systems at the C5 position of the central pyrazine ring exhibited superior AR inhibiting activity relative to the parent botryllazine A. In addition, the benzoyl groups at positions C2 and C3 of the pyrazine ring were dispensable for this improved inhibitory activity. Conversely, a benzoyl group-containing phenolic hydroxyl groups-at either position C2 or C3 of the pyrazine ring was essential for attainment of high inhibitory activity approaching that of sorbinil (a highly effective AR inhibitor).

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Section: Resultsmentioning

confidence: 99%

Synthesis and Aldose Reductase Inhibitory Activity of Botryllazine A Derivatives

Saito

Ishibashi

Noumi

et al. 2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…followed by exposure to N ‐(2‐pyridyl)bis(trifluoromethanesulfonamide) gave corresponding enol triflate 5 in 79 % yield. This compound was subjected to palladium‐catalyzed reduction under our previously established conditions (91 %),21 and resulting cyclohexene 6 was oxidized by reaction with manganese triacetate/ tert ‐butyl hydroperoxide22 to give cyclohexenone 7 in 73 % yield. This can be converted into (+)‐aspidospermidine ( 8 ) as described in the literature,23 and hence the formal synthesis of this natural product has been completed 24…”

Section: Resultsmentioning

confidence: 99%

Enantioselective Synthesis of Quaternary Carbon Stereogenic Centers through the Primary Amine‐Catalyzed Michael Addition Reaction of α‐Substituted Cyclic Ketones at High Pressure

et al. 2015

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The enantioselective Michael addition reaction of α‐substituted cyclic ketones with acrylates was efficiently promoted by a primary amine chiral catalyst under high‐pressure conditions (1.0 GPa) in tetrahydrofuran. This method was highly successful for the construction of an all‐carbon‐substituted quaternary‐carbon stereogenic center at the α‐position of cyclic ketones in high enantiomeric excess, and could be conveniently applied to the formal synthesis of (+)‐aspidospermidine.

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“…Success was achieved when 10% palladium acetate, 10% diphenylphosphinopropane (dppp) and 2.5 equ. of triethylsilane25 at 60°C for 4 h was used to produce the desired morphinones ( 17–19 , Table 1). …”

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Rapid access to morphinones: removal of 4,5-ether bridge with Pd-catalyzed triflate reduction

Hupp

Neumeyer

2010

Tetrahedron Letters

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A new synthetic method for the removal of the 4, 5-bridged ether moiety of several opioids has been developed. This process offers a faster, simpler synthetic route to obtain the morphinone scaffold in high yields without the need for protection of the ketone moiety. Keywords morphinone; opioid; 4, 5-ether bridge; triflate reduction Opioids such as morphine (1) and codeine (2) (Figure 1) and analogs offer a wealth of therapeutic benefit as analgesics and as building blocks for valuable therapeutics. 1-3 Opioid analgesics such as hydrocodone (3) and oxycodone (4) (Figure 1) are used to treat intense pain 1 while the opioid, naltrexone (5 , Figure 1), is used to aid in reducing opioid dependence. [4][5][6] More facile synthetic methods to gain access to new opioid analogs can offer the opportunity to discover potentially useful opioid therapeutics.Opioids without the 4, 5-ether bridge (referred to as morphinones, Figure 1) are of particular interest due to their novel biological and pharmacological properties. [7][8][9][10][11] The only reported method used today to remove the 4,5-ether bridge 7-13 was originally described by Sawa and coworkers in the 1960's and uses ammonia gas and solid sodium metal. 14,15 This synthetic route involves multiple steps, including protection and deprotection of the ketone moiety, resulting in a low overall yield of the final morphinone product. 7-15 A shorter, higher yielding alternative route to these intriguing compounds would be quite valuable and necessary to access the morphinone scaffold efficiently making them readily available for pharmacological and biological evaluation.In a continuing effort in our laboratory to synthesize novel kappa opioid agonists and mixed kappa/mu agonists for the treatment of drug abuse, 11,16-22 we have developed an efficient synthetic route that allows easier access to this pharmacologically important class of compounds. Our method for the synthesis of the morphinone scaffold includes a palladium Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Supplementary MaterialSupplementary data associated with this article includes experimental details and characterization for compounds 7-19. This information can be found in the online version. The opioid-4-triflates used in the palladium catalyzed reduction were synthesized according to Scheme 1, shown below. The phenol moiety of naltrexone (5) and naloxone (6) was methylated using iodomethane and potassium carbonate to yield derivatives 7 29 and 8, respectively. Hydrocodone (3), oxycodone (4), 7 and 8 were then reduced to their phenol derivatives (9-12) usi...

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An Efficient Procedure for Palladium-Catalyzed Reduction of Aryl/Enol Triflates

Cited by 61 publications

References 0 publications

Synthesis and Aldose Reductase Inhibitory Activity of Botryllazine A Derivatives

Synthesis and Aldose Reductase Inhibitory Activity of Botryllazine A Derivatives

Enantioselective Synthesis of Quaternary Carbon Stereogenic Centers through the Primary Amine‐Catalyzed Michael Addition Reaction of α‐Substituted Cyclic Ketones at High Pressure

Rapid access to morphinones: removal of 4,5-ether bridge with Pd-catalyzed triflate reduction

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