C h r o m a n -2 -o n e s b y R e d u c t i o n o f C o u m a r i n sAbstract: The scientific literature detailing the synthesis of chroman-2-ones by hydrogenation/reduction of the corresponding coumarins is reviewed. The following methods are described: hydrogenation on palladium, platinum, nickel, catalytic transfer hydrogenation, homogeneous hydrogenation, reduction by complex hydrides, reduction by metals, and electrochemical reduction. For each appropriate reaction, the yield, duration and some additional information is given (if available). Moreover, many exceptions and interesting transformations are described.
NaBHT(sodium 2,6-di-tert-butyl-4-methylphenolate), a strong, but hindered and lipophilic base, has been effectively paired with similarly lipophilic, highreactivity Pd-NHC (N-heterocyclic carbene) catalysts to produce an ideal combination for performing solvent-free (melt) cross-coupling amination. The mild nucleophilicity of NaBHT, coupled with the anti-oxidant properties of its conjugate acid byproduct, BHT means the process seems to have no functional group incompatibilities. Highly effective coupling of base-sensitive and redox-active functional groups was observed in all cases with only 0.1-0.2 mol percent catalyst. Comparisons using the standard base for this reaction, KOtBu, led to poor couplings or complete degradation in most applications -only NaBHT works.As all businesses struggle to achieve a zero-carbon footprint, the fine-chemical manufacturing sector faces unique challenges. Commodity chemical companies such as those in the petrochemical [1] and polymer sectors, [2] are actually quite efficient in terms of atom-economy and produce relatively little waste. Conversely, companies that conduct traditional organic synthesis, such as those in the agrichemical, pharmaceutical, and electronics sectors, produce waste that dwarfs the actual quantity of the final target. This can be evaluated in a number of ways, but one of the most common metrics used is the process 'E-Factor' (Environmental Factor), [1] which is a ratio of the mass of waste produced relative to the desired product. This number is shockingly high for fine chemical and pharmaceutical manufacturing, often surpassing a value of 100 for many processes. [1,3] A major contributor to E-Factor is organic solvent and chemists have primarily looked to reduce the waste produced from reaction solvent by trying to adapt processes to tolerate water as the solvent, [1,4] or to avoid reaction solvent all together by performing the transformation solvent free. [1,5] If all reaction components, including products and byproducts, are liquids, then neat transformations are somewhat more straightforward because the reaction components all serve the role as solvent for each other. Conversely, if one or more of the reaction components are solids, instead of forming a homogeneous solution, the reaction takes on a paste-like consistency making uniform distribution of the reaction components difficult. This is especially challenging for reactions that are performed catalytically, in particular when the use of as little catalyst as possible is desired to enhance process efficiency and 'greeness'.Not only does the insolubility of the catalyst negatively impact reactivity in melts, poorly soluble, critical additives, such as bases and salts, [6] also inhibit conversion. In amination, the base is essential to generate the metal amide that is necessary to undergo reductive elimination and complete the catalytic cycle; base strength (pKb) and solubility are key in this respect. Very strong bases like tert-butoxide are very effective at deprotonating the metal-ammonium...
Catalytic homogeneous hydrogenation of 7-methoxy-3-phenylchromone and other substrates was achieved in the presence of cationic iridium complexes and base as co-catalyst. Contrary to common alkene hydrogenation, which is inactivated by base, the hydrogenation of the above set of electron-deficient alkenes turned out to be base-activated.Hydrogenation is one of the most important classes of organic reactions. The enormous potential of the homogeneous metallocomplex-catalyzed hydrogenation is commonly acknowledged and numerous applications towards preparation of a wide range of organic compounds are presented in the recently published three-volume set The Handbook of Homogeneous Hydrogenation. 1 It has to be emphasized that this versatile method is especially valuable for the enantioselective reduction 2 of alkenes, ketones, imines etc, and is used both in laboratory and in industry. 3Base treatment (i.e., Et 3 N) enhances the catalytical activity of rhodium complexes forming neutral coordinatively unsaturated hydrido complexes. 4 Unlike rhodium, iridium is known to be deactivated by organic bases. 5,6Hereby we want to report a completely new type of homogeneous hydrogenation, catalyzed by iridium complexes and activated by base. Several complexes of rhodium ([Rh(PPh 3 ) 3 Cl], [Rh(BI-NAP)(COD)Cl], [Rh(BINAP)(COD)]OTf) and those of ruthenium ([Ru(PPh 3 ) 3 Cl 2 ], [Ru(p-cymene)(BINAP)-Cl]Cl, [Ru(BINAP)(OAc) 2 ]) were found to be inactive towards homogeneous hydrogenation of 7-methoxyisoflavone (1) under pressure of hydrogen (100 bar) in various solvents (toluene, THF, dichloromethane, DMF, 2-propanol, methanol) with or without activation by base or acid. Transfer hydrogenation, catalyzed by [Ru(pcymene)(Tsen)Cl]Cl 7 (Tsen = N-Tosylethenylendiamine) was also ineffective for this substrate.Complex 3 was not able to perform a homogeneous hydrogenation of 1 under standard conditions in toluene or dichloromethane. 8 However, the corresponding chromanone 2 was detected after hydrogenation in the presence of triethylamine (Scheme 1).In order to explain this unexpected result, we need to take the structure of both the substrate and catalysts into account. Iridium complexes of type [Ir(cod)(L) 2 ]X or [Ir(cod)(L^L)]X (where cod = 1,5-cyclooctadiene, L^L = chelating ligand, and X = a noncoordinating anion) are precatalysts. They are activated by hydrogenation of coordinated 1,5-cyclooctadiene to form extremely electrophilic species. 9 These can coordinate to double bond, add and transfer hydrogen. 9 It is also well known that isoflavones react with electrophiles to give 8-substituted chromones as the products of normal electrophilic substitution in the aromatic ring. 10 The C=C bond in the chromone ring of isoflavones is known to be very electron-deficient. Therefore it is inert towards electrophiles and rather apt to react with nucleophiles, 10 presumably including the base-activated catalyst 3, hence the 'nucleophilic homogeneous hydrogenation'.In order to optimize the reaction conditions, base-and solvent-screening experi...
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