Mediated Reductions

LY311727 is an indole acetic acid based selective inhibitor of human non-pancreatic secretory phospholipase A2 (hnpsPLA2) under development by Lilly as a potential treatment for sepsis. The synthesis of LY311727 involved a Nenitzescu indolization reaction as a key step. The Nenitzescu condensation of quinone 4 with the p-aminoacrylate 39 was carried out in CH3NO2 to provide the desired 5-hydroxylindole 40 in 83% yield. Protection of the 5-hydroxyl moiety in indole 40 was accomplished in H2O under phase transfer conditions in 80% yield. Lithium aluminum hydride mediated reduction of the ester functional group in 41 provided the alcohol 42 in 78% yield. 

Intlium-mediated reductive cyclizadon of 2-nitroacylben2enes into 2,Tbetmsoxa2oles in... 

A general method for the synthesis of N-unsubstituted aziridine-2-carboxylates involves a triphenylphosphine-mediated reductive cyclization of hydroxy azido esters [17-22]. A recent example involves the treatment of [1-hydroxy-a-azido ester 15 (Scheme 3.6) with PPh3 to give aziridine 16 in 90% yield [19]. a-Hydroxy- 3-azido esters undergo similar reactions to give aziridine-2-carboxylates [20-22],... 

Scheme 1. Generality of the titanium mediated reductive cyclopropanation of N,N-diakylcarboxamides. More than 60 compounds have been prepared by this route.

Kaneko C., Katagiri N., Nomura M., Sato H. A New Method for the Stereoselective Synthesis of Nucleosides by Means of Sodium Borohydride Mediated Reductive C-C or C-N Bond Cleavage Reaction Isr. J. Chem. 1991 31 247-259 Keywords carbohydrates... 

A general synthesis of pyrrolo[3,4-with amidines. The suggested mechanism is that shown in Scheme 2 < 95JOC7687 >. 

In 2009, Chirik reported a hydrogen-mediated reductive enyne cyclization catalyzed by the bis(imino)pyridine iron complex 5 (Scheme 37) [119]. In the... 

Reduction of monocyclic aromatic nitro compounds has been demonstrated (a) with reduced sulfur compounds mediated by a naphthoquinone or an iron porphyrin (Schwarzenbach et al. 1990), and (b) by Fe(II) and magnetite produced by the action of the anaerobic bacterium Geobacter metallireducens (Heijman et al. 1993). Quinone-mediated reduction of monocyclic aromatic nitro compounds by the supernatant monocyclic aromatic nitro compounds has been noted (Glaus et al. 1992), and these reactions may be signihcant in determining the fate of aromatic nitro compounds in reducing environments (Dunnivant et al. 1992). 

Cell-free supernatants may mediate reductions. The reduction of aromatic nitro compounds by SH was mediated by the hltrate from a strain of Streptomyces sp. that is known to synthesize 2-amino-3-carboxy-5-hydroxybenzo-l,4-quinone (cinnaquinone)... 

Glod G, W Angst, C Holliger and RP Schwartzenbach (1997) Corrinoid-mediated reduction of tetrachloro-ethene, trichloroethene, and trichlorofluoroethene in homogeneous solution reaction kinetics and reaction mechanisms. Environ Sci Technol 31 253-260. 

Schwarzenbach RP, R Stierliu, K Lanz, J Zeyer (1990) Quinone and iron porphyrin mediated reduction of nitroaromatic compounds in homogeneous aqueous solution. Environ. Sci. Technol. 24 1566-1574. 

Lloyd JR, VA Sole, CVH van Praagh, DR Lovley (2000) Direct and Fe(II)-mediated reduction of technetium by Fe(III)-reducing bacteria. Appl Environ Microbiol 66 3743-3749. 

Crocq et al. (1997) have synthesized trimegestone through Bakers yeast mediated reduction of a ketone (this material is a new progestomimetic molecule for the treatment of postmenopausal diseases). The key step of the multistep synthesis is the chemo-, regio- and almost stereospecific bioreduction of a triketone to the desired alcohol. 

Scheme 11.6 gives some examples of the various substitution reactions of aryl diazonium ions. Entries 1 to 6 are examples of reductive dediazonization. Entry 1 is an older procedure that uses hydrogen abstraction from ethanol for reduction. Entry 2 involves reduction by hypophosphorous acid. Entry 3 illustrates use of copper catalysis in conjunction with hypophosphorous acid. Entries 4 and 5 are DMF-mediated reductions, with ferrous catalysis in the latter case. Entry 6 involves reduction by NaBH4. 

Dithionite-mediated reductive activation of mitomycin C has been employed in the study of its DNA alkylation chemistry.6,63 However, dithionite activated mitomycin C possesses different DNA alkylation properties than that activated by catalytic hydrogenation and enzymatic reduction. We postulated that a new alkylating species is produced by dithionite reductive activation resulting in different reactivity than the iminium methide species. To investigate dithionite-mediated reductive activation further, we treated 13 C-labeled analogues of WV-15 with dithionite and carried out spectral and product studies. 

Zinc-mediated reductive dimerization cyclization of 1,1-dicyano-alkenes occurs to give functionalized cyclopentenes in good yields under saturated aqueous NH4CI-THF solution at room temperature. The trans isomers are the major products (Eq. 10.38).89... 

To our knowledge, the first examples of catalytic non-hydrogen-mediated reductive C-C bond formation involve the reductive dimerization (telomeriza-tion) of butadiene mediated by silane, see Ref. 6-12. 

Scheme 6 Complementary regioselectivities in direct aldol couplings of 2-butanone and corresponding hydrogen-mediated reductive aldol couplings of MVK...

Scheme 18 Hydrogen-mediated reductive aldol reaction...

Metal-mediated reductive coupling of alkenes and alkynes affords access to complicated organic structures, including carbocyclic and heterocyclic molecules, from readily available starting materials. While most of these coupling reactions were initially developed as stoichiometric processes, many selective, catalytic versions have been developed over the past decade these advancements have made reductive coupling much more attractive to synthetic chemists. 

Scheme 35 Mechanism of the arylboronic acid-mediated reductive cydization...

Weber EJ, Adams RL (1995) Chemical- and sediment-mediated reduction of the azo dye disperse blue 79. Environ Sci Technol 29 1163-1170... 

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