Medium-sized heterocycle synthesis

Tanaka and Ohno developed the palladium(0)-catalyzed cyclization of bromoallene 222 bearing a sulfonamide for the synthesis of medium-sized heterocycle 223 (Scheme 37).48b In this reaction, bromoallene acts as an allyl dication equivalent 224, and two different nucleophiles can be introduced regioselectively. The intramolecular nucleophilic... 

The two-carbon ring expansion which involves the [2 + 2] cycloaddition of enamines of cyclic ketones with electron-deficient acetylenes followed by thermal rearrangement of the resulting fused cyclobutenes (see Section II.E) has been successfully used in the synthesis of medium-size heterocycles. Examples include the preparation of compounds 407246, 408247 and 409248. 

Metal-mediated synthesis of medium-sized heterocycles 00CRV2963. 

Synthesis of medium-sized heterocycles by the ring-closing metathesis reaction 00AG(E)2079. 

To demonstrate the versatility of this process and to provide a relevant model study for the synthesis of 1, we investigated an extension to medium-sized heterocycles. Thus, the diastereomeric silyl ethers 8a-b were selected to test this application by generation of the corresponding 9-membered oxacyclic dienes (Scheme 3). The preparation of 8a-b began with the reduction of pyruvic aldehyde dimethoxy acetal with NaBH4 in MeOH/THF to afford hydroxy acetal 2 (84%). Alkylation of the sodium salt of 2 with propargylic bromide afforded 3 (85%). Conversion of 3 to 5 was achieved by alkyne iodination followed by a c/s-reduction of... 

Neat exploitations of this process, include the synthesis of medium-sized heterocycles as products of a three stage sequence involving addition of hydroxide to w-iodoalkyl thiazolium salts, ring-opening and then reclosure by intramolecular S-alkylation, illustrated below for the formation of an eight-membered ring, " and the introduction of sulfur to the imidazole 2-position using phenyl chlorothionofor-mate. ... 

Quite a number of variations of this process have been reported in the past, for example, for the synthesis of medium-sized heterocycles.f" - ... 

Ohno H, Hamaguchi H, Ohata M, Kosaka S, Tanaka T (2004) Palladium(0)-catalyzed Synthesis of Medium-Sized Heterocycles by Using Bromoallenes as an Allyl Dication Equivalent. J Am Chem Soc 126 8744... 

We summarized some of the recent examples dealing with the synthesis of medium-sized heterocycles featuring a key stereoselective MBFT. Medium-sized rings are key structural subunits found in many bioactive natural products and synthetic compounds. Therefore, the search for general, versatile, and efficient methods with high regio and stereoselectivity is, and will continue to be, an active research field. 

RCM reaction had major impact in the field of medium ring-sized heterocycle synthesis as demonstrated by numerous publications in this area [60,61]. However, the reaction also suffers from many of the drawbacks of common organic transformations, and thus has drawn attention for greener applications. Grubbs and coworkers developed a highly active water-soluble olefin metathesis catalyst of the type 99 (Figure 5) for this purpose [62]. 

Fig. 16 Synthesis of medium-sized benzo-fused heterocycles through tandem Ugi-SNAr processes...

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