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Oxidative ring cleavage reactions of furans constitute a group of important transformations that have found wide utility in synthetic organic chemistry. These processes have been used to prepare a variety of 1,4-dicarbonyl compounds including 1,4-dioxoalkenes, 4-oxoalkenals, 4-oxoalkenoic acids, and their derivatives such as 4-hydroxybutenolides and 2,5-dialkoxydihydrofurans. Oxidations of furfuryl alcohols (Achmatowicz reaction) and furfuryl amines (aza-Achmatowicz reaction) provide access to highly functionalized heterocyclic structures that have been employed as intermediates in synthetic routes for the preparation of complex molecules including carbohydrates and alkaloids. Complete oxidative degradation of the furan ring affords carboxylic acids; thus the oxygen heterocycle has served as a masked carboxyl group in many synthetic studies. These transformations and their applications in total syntheses are covered in this chapter. Keywords: Furan; Oxidation; 1,4-Dicarbonyl Compounds; 4-Oxoalkenals; 4-Oxoalkenoic Acids; Carboxylic Acids; Ozone; Singlet Oxygen; Ruthenium Tetroxide; Singlet oxygen; 4-Hydroxybutenolides; Achmatowicz Reaction; Hydrogen Peroxide; N-Bromosuccinimide; tert-Butylhydroperoxide; meta-Chloroperbenzoic Acid; Magnesium Monoperoxyphthalate

A novel method allows the synthesis of 1,2-diketones under mild conditions through nitroxyl-radical catalyzed oxidation of silyl enol ethers with magnesium monoperoxyphthalate as the oxidant.

Whereas the oxidative cleavage of bicyclic isoxazolidines 5 (2-phenylperhydroisoxazolo[2,3-a]pyridine) and 9 (6-(2-benzyloxyethyl)- 8 -(3-phenylsulfonylpropyl)-7 -oxa-1-azabicyclo-[3.2.1]octane) with magnesium monoperoxyphthalate (MMPP) significantly favours the formation of the more substituted tetrahydropyridine N-oxides, 3-chloroperoxybenzoic acid (mCPBA) is shown to favour the less substituted nitrone 10 in reaction with the more substituted isoxazolidine 9.

Treatment of N-alkyl-N-allenylmethylanilines with magnesium monoperoxyphthalate in methanol–water underwent tandem transformations to furnish N-alkyl-2-ethenylindoles in good yield.

Dialkylfurans were reacted with magnesium monoperoxyphtalate (MMPP) in methanol to give 2,5-dimethoxy-2,5-dihydrofurans in high yields under mild reaction conditions.

Biomimetic oxidation of unactivated arenes with magnesium monoperoxyphthalate and a fluorinated iron porphyrin as catalyst lead mainly to p-quinones without involving phenols as reaction intermediates.

Optically active α- and α,β-substituted aldehyde hydrazones 2, 4, and 7, which are readily available by asymmetric alkylation. Michael addition or [2,3]-Wittig rearrangement of chiral hydrazones can be transformed into nitriles 3 and 5 or cyanohydrins 8 by MMPP mediated oxidation, respectively. This synthetic sequence offers a C-C connective entry into optically active functionalised nitriles with good overall yields (30—75 %) together with high diastereo- and enantioselectivities (de = 76-≥ 96%. ee72- ≥97%).

Isovanillin was oxidized with magnesium monoperoxyphthalate to 4-methoxyresorcinol (2) and the latter was reacted with 3-oxo-propionic acid ethylester prepared in situ to give scopoletin (1). These reactions can be achieved in kg scale in high yields.

A variety of unsubstituted and mono- or di-substituted cycloalkanones can be oxidised with modest excess of magnesium monoperoxyphthalate hexahydrate in acetonitrile to produce the corresponding lactones in a facile, selective, and high yielding manner.

A simple, efficient and chemoselective, non-aqueous procedure for oxidation of sulfides to the corresponding sulfones with magnesium monoperoxyphthalate on hydrated silica gel has been developed.

The selective oxidative cleavage of the SAMP-hydrazone moiety of 4-silyloxy-3-enal hydrazones 6 , leading to the corresponding 4-silyloxy-3-alkenenitriles 7 , is reported. A clean, good yielding transformation was observed when m -CPBA in CH 2 Cl 2 was used as the oxidant, the presence of suspended solid NaHCO 3 being essential in preventing hydrolysis of the silyl enol ether moiety. Use of magnesium monoperoxyphthalate (MMPP) led to over-oxidated products, while hydrogen peroxide, in the presence of catalytic methyltrioxorhenium (MTO), was ineffective. Independent measurements of the enantiomeric excesses for compounds 7 demonstrated the absence of racemization during the process.

Unsupported, moist magnesium monoperoxyphthalate (MMPP) was found to oxidize various phosphorus keto ylides to the corresponding vicinal tricarbonyls selectively in dichloromethane at ambient temperature in good to excellent yields.

Magnesium monoperoxyphthalate and urea–hydrogen peroxide–acetic anhydride are effective reagents in the oxidation of benzaldehyde to benzoic acid and o- and p-methoxybenzaldehyde to the corresponding phenols. On the other hand, aromatic aldehydes, including the isomeric methoxybenzaldehydes, are oxidised to the corresponding benzoic acid derivatives in good to excellent yields by the hydroperoxide anion generated from urea–hydrogen peroxide.

Reactions of O-ethyl S-(2-diisopropyl-amino)ethyl methylphosphonothiolate, VX 1, were investigated with five oxidizing agents. In all the cases, the formation of the VX N-oxide 7 was observed prior to the subsequent oxidation and hydrolysis into the nontoxic O-ethyl methylphosphonate 2. Magnesium monoperoxyphthalate (MMPP) is probably one of the most active reagents to achieve the complete detoxification of VX 1. The decontamination using MMPP was also extended with success to soman 13, a G-type agent. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:485–490, 2001

1-(Methyl-p-tolyl-amino)-3-phenoxy-2-azetidinones 4-COX and 4-R substituted (COX: X=Me, Et, Ph, NMe2, NEt2, OBut; R=Me, Et, Ph) were smoothly prepared from the corresponding α-(methyl-p-tolyl)hydrazonylated ketones, amides and esters via [2+2] cycloaddition with phenoxyketene. The reaction was generally high-yielding and diastereoselective, leading to β-lactams with a cis relationship between the PhO and the COX moieties, except for R=Ph, where an opposite stereoselectivity was instead observed. The azetidinones represent interesting intermediates which couple protection at N(1) and functionalization at position 4 of the ring. Deprotection of N(1) can be easily attained by oxidative N–N cleavage with magnesium monoperoxyphthalate.