Applications in Total Synthesis

During recent years, cross metathesis has found a wide range of applications in total synthesis. CM has been the key step in the syntheses of (-)-lasubine 11 [134], (+)-7a-ept-7-deoxycasuarine [135], and melithiazole C [136] to name just a few examples. It has been used for the modification of tetrapyrrolic macrocycles [137] as well as erythromycin derivatives [138], the dimerisation of steroids [139] and the synthesis of prostaglandin analogues [140]. 

A complementary method was reported 3 years later by Hino, in which a readily enolizable diketopiperazine 48 was directly converted to the epidisulfide by deprotonation with sodium hydride and exposure to sulfur monochloride [38]. As with the Trown method, this method was limited to a specific class of substrates, namely, ones possessing a 1,3-dicarbonyl motif at each of the reactive centers, yet it has also seen subsequent applications in total synthesis [39, 40]. In 1972, Schmidt was able to significantly broaden the scope of the enolate thiolation method by introducing elemental sulfur as the electrophilic agent [41]. In contrast to Hino s method in which formation of a highly reactive, unstable adduct requires readily... 

Allenylsilanes 159 (Eq. 13.53) and 161 (Eq. 13.54) differ in the axial stereochemistry of the allene function. In each case, formation of the benzyl imine, followed either by treatment with tin(IV) chloride in benzene at room temperature or heating in toluene, leads to diastereomeric products 160 and 162 [63], Significantly, there is no crossover, pointing to a concerted (or fast, stepwise) process. Since the absolute stereochemistry of the allenylsilanes is easily controlled, the methodology is ideal for applications in total synthesis. Weinreb and co-workers have used the reaction for his synthesis of the marine natural product (-)-papuamine. 

For applications in total synthesis this method was also thought to be applicable to chiral aldehydes, leading to matched and mismatched situations. Therefore, vinylogous ketene acetal 40 was put to reaction with chiral aldehyde 44 and both enantiomers of Carreira s catalyst. Reaction of aldehyde 44 with the (S)-Tol-BINAL-CuF catalyst (matched case) produced only one diastereomeric... 

The Shi epoxidation has found several applications in total synthesis [15]. Particularly attractive are examples in which it has been used to establish the stereochemistry of polyepoxides which can undergo cascade cyclizations to polyether products, mimicking possible biosynthetic pathways. An example is the construction of the tetahydrofuran rings of the natural product glabrescol via highly stereoselective formation of the tetraepoxide 10 from the polyene 9 (Scheme 12.6) [22]. 

The efficiency of the carbene-based systems has led to their application in total synthesis. For example, Andrus and co-workers [74] recently reported a new synthetic approach to resveratol, the probable causative agent of the French paradox [75]. A decarbonylative Heck reaction was the key step of this concise and cost-effective synthesis [76-78]. 

Applications in Total Synthesis. Two recent examples of directed hydrogenations employing (1) in the total synthesis of complex molecules are illustrated. In eq I a simultaneous diastereoselective reduction of the trisuhstituted alkene and the a,p-unsaturated ester afforded the illustrated advanced intermediate in the asymmetric total synthesis of ionomycin. In addition, a two-directional application has been utilized in an asymmetric synthesis FK-506 (eq 2). ... 

Syntheses of 2,6-dialkyl-1,2,5,6-tetrahydropyridines and their applications in total synthesis 04MI23. 

Figure 5 (a) Development of pyridine-based catalysts (b) hydrogenation of selected model substrates and (c) selected application in total synthesis... 

The thioamide can accommodate a number of functional groups since alkylation proceeds under mild conditions, i.e. neutral solutions at room temperature. For example, the presence of a sulfide did not interfere with alkylation on the thioamide (equation 4). The range of functional groups compatible with this reaction will become evident in the discussion of its applications in total synthesis (Section 3.7.4). 

Asymmetric Transition Metal Catalyzed Allylic Alkylations Applications in Total Synthesis ... 

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