Reduction Fukuyama

Aldehyde synthesis through reduction of thiol esters with EtsSiH in the presence of Pd/C catalyst. 

Kimura, M. Seki, M. Tetrahedron Lett. 2004,45, 3219. (Possible mechanisms were proposed in this paper). 

J J Li Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI10 1007/978-3-319-03979-4 113, Springer International Publishing Switzerland 2014 

Shimada, K. Kaburagi, Y. Fukuyama, T. J. Am. Chem. Soc. 2003,125,4048-4049. Kimura, M. Seki, M. Tetrahedron Lett. 2004, 45, 3219-3223. (Possible mechanisms were proposed in this paper). 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 105, Springer-Verlag Berlin Heidelberg 2009 

Synthesis of primary amines using potassium phthalimide and alkyl halides. 

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The Fukuyama Reduction allows the convenient and selective reduction of thioesters, which are easily prepared from the corresponding carboxylic acids, for example by the Steglich Esterification. 

Compared to other direct reductions of carboxylic acids or carboxylic acid derivates such as using DIBAL-H or Rosenmund conditions, the Fukuyama Reduction is a mild alternative, offering outstanding functional group tolerance. 

Fukuyama reduction is a mild method for the conversion of thioesters to aldehydes in the presence of other susceptible functional groups, including amides, esters, lactones, and acetonides. Review Fukuyama, T. Tokuyama, H. Aldrichimica Acta 2004, 37, 87-96. 

The synthesis of the E-ring 476 started with aldehyde 473, prepared via boron-mediated aldol reaction. FeUdn-selective Lewis acid-catalyzed aldol reaction of 473 with thioketene acetal afforded a-alcohol 474 (dr = 94 6). Fukuyama reduction of thioester to aldehyde followed by hemiacetalization and TBS protection furnished the E-ring 475, which was converted into phenylsulfone 476 in standard fashion. 

Carboxylic acids are reduced to aldehydes via the ester and DEAL, via the acid chloride in the Rosenmund reduction and via the thioester in the Fukuyama reduction. 

Thioesters are reduced selectively to aldehydes by the Fukuyama reduction [34], shown in Equation 6.20 [35]. Even the alkene functionality can be preserved in this reaction by the use of Lindlar s catalyst and a sacrificial alkene as shown in Equation 6.21 [36]. 

Like the mitomycins, FR900482 (6), FR66979 (7), FK973 (8), and FK317 (9) have also been shown to crosslink DNA both in vivo [68-70], and in vitro after reductive activation [71-76] with selectivity for the 5 -CpG-3 sequence [77]. The mechanism outlined in Figure 11.2 was originally proposed by Goto and Fukuyama [78] and has been verified by the experimental work of Williams and Hopkins [71-77, 79]. Reduction of the N-O bond produces intermediate 27, which can lose a molecule of water to form 28, which reacts with DNA by a mechanism similar to that found... 

Thiol esters undergo smooth reduction to give aldehydes by the Fukuyama hydrosilylation procedure, which is an alternative way to transform carboxylic acids to aldehydes. Upon treatment with Et3SiH and 10% Pd/C, a thioester underwent smooth reduction to give an aldehyde.409,410 For example, to a stirred mixture of thioester and Pd/C in acetone may be added Et3SiH at room temperature under an Ar atmosphere. Stirring is continued until the hydrogenolysis is complete (0.5-1 h) (Scheme 4.117). 

A palladium-catalysed reduction of ethyl thiolesters to aldehydes with triethylsilane has been proposed by Fukuyama [2611. The reaction, coupled with a mild conversion of carboxylic acids to thiolesters (see [261], footnote 2), affords a versatile method for the overall transformation of... 

The preparation of protected (/ )-2-methyl-cysteine by Fukuyama starts with the enantio-selective discrimination of the prochiral ester groups in 6 with pig liver esterase (Scheme 3) [5]. The ester function of the resulting product 7 is selectively reduced (7 16). Cyclization to the )9-lactone gives compound 17. Attack of the thioacetate at the )9-lactone methylene carbon atom provides the (/f)-compound 18. Selective reduction of the carboxylic acid function in 7 gives the (S)-compound 19 in an analogous fashion. 

Fukuyama and Yung (81TL3759) used adduct 69 as a key starting material for the synthesis of methyl ( )-3-(3-cyana-6-oxabicyclo[3.I.0]hex-2-en-5-yl)-2-propenoate (81). The reaction of cycloadduct 69 with methyl lithioacetate gave unsaturated ester 77. Reduction in acidic media of the conjugated double... 

In 1990, Fukuyama and co-workers established a palladium-mediated reduction of thiol esters to aldehydes with Et3SiH (Eq. 19) [40]. 

As outlined in Scheme 6, isovanillin (35) was converted to aryl iodide 36 via MOM-protection, protection of the aldehyde, and subsequent iodination. Hydrolysis of the acetal and Wittig olefination delivered phenol 37 after exposure of the intermediate aldehyde to methanolic hydrochloric acid. Epoxide 41, the coupling partner of phenol 37 in the key Tsuji-Trost-reaction, was synthesized from benzoic acid following a procedure developed by Fukuyama for the synthesis of strychnine [62]. Birch reduction of benzoic acid with subsequent isomerization of one double bond into conjugation was followed by esterification and bromohydrin formation (40). The ester was reduced and the bromohydrin was treated with base to provide the epoxide. Silylation concluded the preparation of epoxide 41, the coupling partner for iodide 37, and both fragments were reacted in the presence of palladium to attain iodide 38. 

Funk s synthesis in 2004 [28] of perophoramidine (Scheme 3), commenced with a base-catalyzed coupling reactiOTi between indole 19 and 3-bromoindolin-2-one 20. Boc protectiOTi of the resulting lactam 21 followed by reduction of the azido functionality led to transamidation and closure of the resulting carbamate upon the indolenine to deliver the aminal 22. Chemoselective chlorination and protection of the lactam followed by a two-step deprotection and conversion of the resulting alcohol to the azide afforded amide 23. A second transamidation reaction followed by selective methylation gave lactam 24. Treatment of lactam 24 with Meerwein s reagent gave imidate 25, which imderwent a Fukuyama deprotection of the sulfur... 

In 2006, Fukuyama and coworkers reported their independent synthesis of yatakemycin (150) [64]. The preparation of the left-hand fragment 165 started with dimethoxybenzene derivative 161. Dibromination of 161 in the presence of FeCls, removal of the TFA group, and oxidation provided a dihydroisoquinoline. Treatment with NsCl to form the hemiaminal, and reductive opening using NaBIl, gave cycUzatiOTi precursor 162. Amination using Cul to give the desired indoline. 

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