Alkynes synthetic targets

Depending on the synthetic target, the zirconium metallacycle does not need to be isolated, and one pot syntheses can be carried out. Addition of n-butyllithium to a THF slurry of Cp2ZrCl2 at —78 °C in the presence of the relevant alkyne, followed by warming to room temperature, generates zirconacycles. Dropwise addition of an hexane solution of a dichloride derivative of main group elements to this solution leads to a variety of heterocycles. 

On account of their very important biological activity, /9-lactams are important synthetic targets [4-9]. Fused polycyclic -lactam subunits appear in many natural products such as penicillins [4-6] and trinems/tribac-tams [10-13]. Fu et al. reported that such frameworks can be prepared with high levels of enantioselectivity via the intramolecular Kinugasa reaction [ 14, 15] of alkyne-nitrone in the presence of a planar chiral Cu/phosphaferrocene-oxazoline catalyst [16]. For instance, compound 1 was transformed into tricyclic /9-lactam 3 in good stereoselectivity and yielded (88% ee and 74% yield) using 5 mol % of CuBr and 5.5 mol % of complex 2 (Scheme 1). 

Besides processes (1) and (2), the reader should be aware that nucleophilic attacks on alkynes are treated in other chapters of this book, dealing with rearrangements, cyclizations, polyacetylenes, cyclic acetylenes and perhaps others. A number of publications overlap with ours in different ways and at different levels -. They treat individual alkynes or families " , e.g. acetylene, diacetylenes , acetylene dicarboxylic esters haloacetylenes , alkynyl ethers and thioethers > ynamines , fluoro-alkynes ethynyl ketpnes , nitroalkynes , etc. synthetic targets, e.g. pyrazoles , if-l,2,3-triazoles , isothiazoles , indolizines S etc. reagents, e.g. nitrones , lithium aluminium hydride , heterocyclic A -oxides - , azomethine ylids - , tertiary phosphorus compounds , miscellaneous dipolar nucleophiles - , etc. The reader will appreciate that all of these constitute alternate entries into our subject. 

Marshall has applied the chiral allenylmetal reagents in a number of natural product syntheses [154, 278-280]. The synthetic utility of these reagents is maximized when the alkyne functionality of Marshall s products is used to further elaborate the carbon skeleton of the ultimate synthetic target. This methodology is il-... 

The intermolecular DBR has been used to prepare a variety of interesting synthetic targets. Quayle has reported a formal total synthesis of aflatoxin B2 using the DBR. Reaction of the acetal-containing chromium carbene 45 with an electron rich alkyne occured in 31% yield to give 46, an advance intermediate for the preparation of aflatoxin. 

The synthetic approach to the benzo[fo]furan is similar to that of the thiophenes described in Scheme 39. The synthetic approach was described by Flynn et al. [73], and an example synthesis is given in Scheme 40. The appropriate iodophenol 104 is coupled to the aryl alkyne 111. The intermediate 155 is subsequently cyclized in the presence of an appropriately substituted aryl iodide, e.g., 107 under an atmosphere of carbon monoxide gas, to give the benzo[fr]furan chalcone derivative 156. Deprotection of the hydroxyl produces the target compound 157. 

Pyrrole has also been utilized to some extent as a diene in Diels-Alder reactions to give functionalized 7-azabicylo[2.2.1]heptenes and 7-azabi-cyclo[2.2.1]heptadienes.4 While the synthetic utility of this reaction is limited by the aromatic stability of the pyrrole ring, the use of Lewis acids, electron-withdrawing groups on the pyrrole, alkyne dienophiles, and high pressures have allowed pyrroles to be employed in the synthesis of several azanorbomane targets.4... 

A similar convergent synthetic strategy was applied in our synthesis of annona-cin, using sequential assembly of the three key fragments, aldehyde 29, phospho-nium 30, and alkyne 14 (Scheme 10-9). In this synthesis, the a,p-unsaturated-y-lactone unit was constructed after completion of the linear skeleton. A modified method was applied into the synthesis of segment 3 (Scheme 10-5), in which the six carbons, as well as two chiral centers from D-glucono-8-lactone, were all incorporated into the final target. Therefore, the efficiency of the whole... 

The difficulties with the aldol reaction resulted in the revised synthesis targeting an Af-alkylation of pyrrole 74 and alkyne 76 (Scheme 26). Though pro-pargylic pyrrole 75 was easily accessed, conversitm to 71a was not successful. All attempts to convert the alkyne to the ketone failed, and little or no conversion was obtained. Often the starting material proved completely unreactive and was recovered. Having embarked on two unsuccessful pathways, a third revision of the synthetic strategy was performed. 

ALkynylpalladations of alkynes and allenes followed by reductive elimination not only represent a novel type of organic transformation but also provide synthetically useful routes toward differently substituted enynes, which are useful building blocks for the synthesis of complex organic targets including natural products and biologically important molecules. 

For the final part (Scheme 5.3), the 20-carbon chain of fumonisin Bj was coupled from the Uthium acetylide derived from 273 and the Weinreb amide 279 (233). After enantioselective reduction of the alkynyl ketone 281 (234, 235), the C-10 stereochemistiy was set, followed by benzyl ether formation and acid-catalyzed acetonide removal, to provide diol 282 (236). Using tricarballylic acid dibenzyl ester, the two hydroxy groups were esterified (237) and the hydrogenation of the azide, the alkyne, and the benzylic ethers led to the target product, fumonisin Bj (249). The spectroscopic analysis matched with those of commercial fumonisin Bj and further experiments on the synthetic material showed inhibitoiy activity on sphingoUpid biosynthesis. 

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