Yamaguchi conditions

With both building blocks 103 and 109 in hand, the total synthesis of lb was completed as shown in Scheme 17. Coupling of acid 103 and alcohol 109 under Yamaguchi conditions to give ester 110 and subsequent desilylation followed by chemoselective oxidation provided hydroxy acid 111. Lactonization of the 2-thiopyridyl ester derived from 111 in the presence of cupric bromide produced the macrodiolide 112 in 62% yield, which was finally converted to pamamycin-607 (lb) via one-pot azide reduction/double reductive AT-methylation. In summary, 36 steps were necessary to accomplish the synthesis of lb from alcohols 88 and 104, sulfone 91, ketone 93, and iodide rac-97. 

The bridging A/B-segment 28 is linked as a menthone acetal to the C-ring building block 23 by ester formation following Yamaguchi conditions [11]. A remarkable macrotrans-... 

Regarding the temperature dependence of the formation of oligomers in the macrolide synthesis under Yamaguchis conditions for macrocycles, Seebach et al. 

Syntheses of heterocycles with ring sizes from seven to thirteen have been reported. Medium-sized ring compounds such as lactones 2 are preferentially synthesized exploiting Yamaguchi conditions. In dilute toluene the activated hydroxy acid 1 cydizes in the presence of 4-(dimcthylamino)pyridine, ... 

Fleming and Ghosh also synthesised nonactin by cyclodimerisation of the acid derived from the benzyl ester 343 (=334) using Yamaguchi conditions (Scheme 47) (75). Nonactin was isolated in lower yield than by the linear tetramer method, presumably because of the problem of "dimer" and oligomer formation. 

Shiina and co-workers report the result of coupling reactions carried out by using benzoic anhydride and its derivatives in place of the Yamaguchi coupling reagent.14 These can provide useful alternatives to the conventional Yamaguchi conditions. In... 

The completion of the total synthesis is described in Scheme 78. The Wittig reaction of 552 and 538 effected the coupling, and subsequent deprotection of TMS with KF afforded 41,42-dihydroxy carboxylic acid 553. Yamaguchi conditions effected macrolactonization of 553 in high yield and complete deprotection of the silyl groups afforded 4b and 554 in a ratio of 1 3. Treatment of (-)-23-epi-altohyrtin... 

The resulting ring size (44- vs 46- membered) was simply controlled by the macrolactonization conditions employed without differential C2i and C23 hydroxyl groups protection. Hydrolysis of the terminal methyl ester in 185 gave the acid 188 which selectively esterified, under Yamaguchi conditions [172], the C21 hydroxyl group of the diol 189 obtained by removal of the silylene group in 185. A 2 1 mixture of the desired C21... 

The ABC-ring carboxylic acid 17 and the FGH-ring alcohol 18 were connected under Yamaguchi conditions to give ester 19 (Scheme 28.3). Desilylation with tetra-n-butylammonium Fluoride (TBAF), acid-catalyzed acetal formation with y-methoxyallylstannane 20, and acetal cleavage with iodotrimethylsilane/hexamethyldisilazane prodnced (y-alkoxyallyl)stannane 21. The ester 21 was... 

Having verrucarol (454), the derivative of verrucarinic acid (465), and the half ester of ( ,Z)-muconic acid (456) all on hand, the total synthesis of verrucarin A (380) could be completed in a further five steps. Thus, verrucarol (454) was esterified first with compound 465 and second with compound 460. Then, molecule 467 was desilylated, macrolactonized under Yamaguchi conditions, and finally deprotected to achieve the natural product verrucarin A (380) (Scheme 8.17). 

Sabitha carried out cyclization of the seco-add 43 under the Yamaguchi conditions in a manner similar to the Rao procedure to furnish the eight-membered lactone 44 in almost the same yield (70%) (Scheme 5.14) [59]. 

Pietruszka [75] reported the total synthesis of a series of solandelactones (A-H) by the coupling reaction of the lactone 78, the key intermediate, with side chains 79 and 80 (Scheme 5.27). Lactone 78 was prepared by cyclization of the seco-acid 77 under Yamaguchi conditions in good yield (85%). Finally, the Nozaki-Hiyama-Kishi coupling of the unsaturated lactone aldehyde or its saturated counterpart with the iodide 79 or 80 afforded solandelactones A-H in good yields as separable diastereomeric mixtures (ratio 2 1). 

Aggarwal performed the stereoselective total synthesis of solandelactones E and F by a stereocontrolled allylboration reaction of the eight-membered lactone 83, which was prepared by cyclization of 81 (Scheme 5.28) [76]. Treatment of the seco-acid 81 under Yamaguchi conditions according to the protocol previously established by Martin et al. [73] and Pietruszka [75] for a similar reaction resulted in the formation of the target lactone 82 in good yield. 

Datta reported the formal synthesis of (6a) by preparation of the nine-membered lactone that possesses a cyclopropane moiety as one of the functionalities (Scheme 5.35) [86]. Cyclization of the seco-acid 95 under Yamaguchi conditions... 

Yonemitsu et al. [46] modified the Yamaguchi conditions in which the mixed anhydride is not isolated and DMAP is directly introduced at room temperature from the beginning. Shiina et al. [47] described the use of 2-methyl-6-nitrobenzoic anhydride (MNBA) as an alternative to 2,4,6-trichlorobenzoyl chloride. Pivaloyl chloride [48], trifluoroacetic anhydride [49], AC2O [50], and B0C2O [51] are also employed for the lactonization via mixed anhydride under basic conditions. Furthermore, Yamamoto et al. [52] described the use of Sc(OTf)3 as a Lewis acid. 

Esterification of acid 135 with alcohol 136 under Yamaguchi conditions gave ester 137, which on reaction with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) followed by treatment with DBN furnished the seco-acid 137a (Scheme 6.24). Macrolactonization of 137a under Yamaguchi conditions furnished macrolactone 138, which finally on deprotection of the benzyl groups afforded verbalactone 139. 

Reaction of acid 142 with alcohol 148 under Yamaguchi conditions followed by desilylation and esterification of acryloyl chloride with 149a furnished diene 150 (Scheme 6.27). RCM of 150 with Grubbs first-generation catalyst furnished the bis-lactone 151, which on global deprotection gave synthetic 152, whose spectral data was not concurrent with the reported data. Hence, the synthesis of 152 has distinctly specified that previously elucidated structure was incorrect for acremodiol (Scheme 6.27). 

The synthetic sequence differed from that of (+)-lepadin F in the second-to-last step, whereby installation of a different ester side chain, namely (2 , 4 )-octadienoic acid, under Yamaguchi conditions afforded 343. An ensuing global deprotection afforded both (+)-lepadin G 344 and (+)-5 -epi-lepadin G 345. As before, spectroscopic comparisons of the NMR data sets of our synthetic (+)-lepadin G and (+)-5 -cpi-lepadin G with Carroll s natural (+)-lepadin G sample suggested that the correct relative stereochemistry at C5 should be R for (+)-lepadin G. 

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