Bicyclic aldehyde precursor

In the laboratory of FI. Flagiwara, the first total synthesis of the polyketide natural product (-)-solanapyrone E was achieved. The installation of the pyrone moiety required the addition of the b/s(trimethylsilyl) enol ether of methyl acetoacetate to a bicyclic aldehyde precursor in the presence of titanium tetrachloride. The resulting -hydroxy- -ketoester was oxidized with the Jones reagent to afford the corresponding -diketoester in good yield. 

Six-membered cyclic guanidine 197 was transformed into the corresponding bicyclic guanidine hemiaminal after deprotection of the Cbz and contemporary cyclization on the masked aldehyde function (Equation 4). This product, 198, was then employed in a Biginelli reaction to form a precursor of alkaloid batzelladine F <1999JOC1512>. 

Michael-type condensation of cyanoacetohydrazide (NCCH2CONHNH2, CAH) with 1,3-dicarbonyl compounds gave pyrazolo[3,4-b]pyridines under certain conditions. With l,l,l-trifluoropentane-2,4-dione in the presence of piperidine a 1 3 mixture of pyrazolone 92a and the expected aminopyridone 91a was obtained.15 The bicycle was also obtained from hydrazone (90) or by thermal reaction between its two precursors.32 Reaction of CAH and / -keto aldehydes gave good yields of only bicyclic products 92b,20 whereas ethyl benzoylacetate in the presence of piperidine gave bicycle 92c (Ar = Ph)... 

A short asymmetric synthesis of the 2-ketocarbacepham (27) involving as the initial step for the preparation of the starting piperidone, a hetero Diels-Alder reaction of the benzylimine derived from the enantiomer of Gamer s aldehyde with Danishesky s diene, has been described <02JOC598>. The key cyclization step to form the bicyclic P-lactam system was achieved from a P-amino acid precursor using the Mukaiyama reagent, 2-chloro-A-methylpyridinium iodide. 

The readily available aldehyde (118) has served as a suitable precursor for a number of 6-endo-( al-kenyl)bicyclo[3.1,0]hex-2-enes. For example, treatment of (118) with PhsP —CHC02Me gives a mixture of die bicyclic diene esters (121)-(123) (Scheme 18). In view of the stereospecific nature of the Cope rearrangement process (vide supra), it is highly likely that (121) and (122) are derived by bond reorganization of the initially formed Wittig products (119) and (120), respectively. The ratio of (121) (122) is, therefore, a reflection of the (expected) fact that the Wittig reaction produces primarily the rrans-a,P-un-saturated ester (119). The diene ester (123) is, presumably, formed by partial isomerization of (121) and (or) (122). 

PhenyUh1o)n1tromethane 1s a convenient reagent for the synthesis of derivatives of 3-methylfuranfor the preparation of a-substituted phenylthlo esters via the homologation of aldehydes, and for the preparation of bicyclic g-lactams from monocyclic precursors.4 This method is an adaption of... 

Having assembled the bicyclic framework, attention was directed toward introduction of the diylophile. Deprotection of the masked aldehyde in 46 and 47 was most efficiently accomplished using 70% aqueous acetic acid at 50-60 °C for 5 days (85% and 95% yield, respectively). The dimethyl dicarbamate was subjected to saponification with potassium hydroxide in refluxing ethanol for 1.5 hours, whereafter the in situ oxidation with potassium ferricyanide at 0 °C gave rise to the dizaene 48 in yields ranging from 76-86%. We were gratified to observe that treatment of 48 with triphenylphosphonium methylide in THF at room temperature led to the desired diyl precursor 41 in 56-83% yield. 

Marshall et al. showed that alkenyl aldehydes can be cyclized on acidic silica gel, and the stereochemistry of the bicyclic alcohol product is controlled by the cis or trans geometry of the monocyclic precursor.This... 

These reactions are not limited to the simple oxazine and oxazolines described above. They are readily prepared from aldehydes and amino alcohols. Meyers used this methodology to prepare chiral precursors for use in asymmetric synthesis. When keto-acid 299 was treated with valinol (300), chiral bicyclic lactam 301 was... 

A comprehensive study has investigated multidirectional cyclative cleavage transformations leading to bicyclic dihydropyrimidinones [61]. This approach required synthesis of 4-chloroacetoacetate resin as the key starting material this was prepared by microwave-assisted acetoacetylation of commercial available hydroxymethyl polystyrene resin under open-vessel conditions. This resin precursor was subsequently treated with urea and a variety of aldehydes in a Biginelli-type multi-component reaction, leading to the corresponding resin-bound dihydropyrimidinones (Scheme 16.40). The desired furo[3,4-d]pyrimidine-2,5-dione scaffold was obtained by a novel procedure for cyclative release under the action of micro-wave irradiation in sealed vials at 150 °C for 10 min. 

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