Acetoxy aldehyde

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

Exposure of the silyl enol ethers of aldehydes to peracid in dichloromethane, followed by treatment of the intermediate masked hydroxy aldehyde (c/. (53) to (54) Section 2.3.2.1.3.i) with acetic anhydride and triethylamine, allows isolation of the product a-acetoxy aldehydes in moderate yield. Similarly treatment of the silyl enol ethers with LTA in acetic acid containing potassium acetate effects the same transformation. ... 

Even in the presence of nucleophiles like methanol, these sterically hindered enols only afforded benzofurans under oxidative conditions. Importantly, when stable enols of the Fuson type, which are less sterically hindered in the P-position, were oxidized with one-electron oxidants a-substituted carbonyl compounds 31 and 34 were obtained with water and various alcohols [64]. With acetonitrile, formation of the oxazole 32 was observed. A related example of this chemistry can be found in the context of Fuson s oxidation studies using Pb(OAc)4 [123] that provided the a-acetoxy aldehyde 31c from 30. To explain the products 31 and 34, three different mechanistic hypotheses were advanced (Scheme 3) [64] similar to the ones rationalizing the benzofuran formation. 

Another route to the preparation of a-hydroxy derivatives consists of the transformation of enolates into silyl enolates and their subsequent oxidation. Oxidation of triaLkylsUyl enolates with peroxyacids, most frequently cpba, has been applied for preparation of a-hydroxy- and a-acetoxy aldehydes or ketones. Reactions require mild conditions and generally give good yields of the expected compound . Mechanistic investigations suggest the intermediate formation of epoxides which evolve to the final products via 1,4-sUyl group migration. 

The reaction of (1) with cyclohexene oxide produces the trans-cyclohexanol derivative (6). Acetylation of (6) followed by mercuric ion-promoted hydrolysis afforded the acetoxy aldehyde (7) in 82% overall from cyclohexenc oxide. 

Quartromicins are complex C2 symmetric macrocyclic natural products that have significant activity against a number of human viral targets.The diastereoselective synthesis of the endo- and exo-spirotetronate subunits of the quartromicins was accomplished by W.R. Roush and co-workers. The preparation of the exo-a-acetoxy aldehyde involved the Pummerer rearrangement oi a sulfoxide using acetic anhydride as the activating reagent and NaOAc as the co-catalyst. The yield of this transformation was modest and all attempts to improve its efficiency failed. 

Diels-Alder-based strategy (Scheme 18).90 An analogous route has also been explored by Miller et a/.91 who obtained the acetoxy-aldehyde (152) from the Diels-Alder reaction of 3-methylbuta-l,3-dienyl acetate with 2-methylprop-2-enal. Cyclization of (152) with sodium hydride gave the coumarin derivative (153). Unfortunately, cyclization of the corresponding methyl ketone (154) yielded the chromanone derivative (155) and not the methyl analogue of (153). 

The acetoxy-aldehyde 53 has a 1,7-relationship between the functional groups and there is no well established approach for this relationship. Disconnection to the alkyl halide 55 is appealing as it can be made from THF in one step. It might be coupled to the Grignard reagent 54 provided we protect the CHO group and exchange Mg for Cu. 

Keck et al. have used the lactone annulation procedure developed in their laboratory to install the lactone moiety by reaction of the lithium enolate of methylacetate with a (3-acetoxy aldehyde [108]. The other key steps include a diastereoselective Lewis acid mediated (Z)-crotylstannane aldehyde addition, a highly selective Lewis acid promoted Mukaiyama aldol reaction and an arari-selective Sml2 reduction of a p-hydroxyketone. The preparation of the C8-C15 fragment of (-)-pironetin started with the chelation-controlled addition of (Z)-crotyl tri-n-butylstannane to the (3-benzyloxy-aldehyde 153 in the presence of TiCU [109] to give the... 

It should be mentioned that authors [72] synthesised the acetoxy aldehyde (53) from labdanolic acid (6) in 5 steps in an overall 50 %... 

They obtained the enol acetate (170) in 92% yield, probably, as a mixture of cis- and trans- isomers. Compound (170) was ozonised, and the resulting product was reduced with NaBfLi to the hydroxy acetate (171) which, on the Swem oxidation, afforded the acetoxy aldehyde (172). The... 

A P-Butenolides are prepared by a related sequence of ZnBra-catalysed phenylthioalkylation of ketene bis(trimethylsilyl) acetals followed by oxidation and elimination. 2-Phenylthiobut-2-en-4-olides are prepared by the reaction of an a-acetoxy-aldehyde with the lithium enolate of ethyl phenylthioacetate. The readily prepared 4-hydroxy-( )-alk-2-enoic esters (174) are smoothly converted into substituted butenolides (175) (Scheme 98). ... 

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