Hetero Diels-Alder coupling reaction

Michael addition reactions (Hetero) Diels-Alder Aldol reactions Addition of ZnR2 to RCHO Formation of cyanohydrin Cross coupling... 

Moody and coworkers have employed a biomimetic hetero-Diels-Alder-aroma-tization sequence for the construction of the 2,3-dithiazolepyridine core unit in amythiamicin D and related thiopeptide antibiotics (Scheme 6.243 a) [426]. The key cycloaddition reaction between the azadiene and enamine components was carried out by microwave irradiation at 120 °C for 12 h and gave the required 2,3,6-tris(thi-azolyl)pyridine intermediate in a moderate 33% yield. Coupling of the remaining building blocks then completed the first total synthesis of the thiopeptide antibiotic... 

Diels-Alder type [4 -1- 2] cycloadditions of nonactivated coupling partners have been effected by various transition-metal catalyses [1]. Interestingly, the cationic ruthenium complex 68 catalyzed the intramolecular [4 -1- 2] cycloaddition between alkyne and enone moieties of 97 leading to 98 (Scheme 4.38) [83]. Such a formal hetero Diels-Alder reaction might proceed via a mthenacyclopentene 99 and an oxam-thenacycloheptadiene 100, which is an mthenium enolate species. 

The concise formal total synthesis of mappicine was accomplished using an intramolecular hetero Diels-Alder reaction as the key step by M. lhara and co-workers. Introduction of the necessary acetylenic moiety at the C2 position was achieved by the Sonogashira cross-coupling of a 2-chloroquinoline derivative with TMS-acetylene. Several substituents at the C3 position were investigated, and it was found that the unprotected hydroxymethyl substituent gave almost quantitative yield of the desired disubstituted alkyne product. 

TiCl4 is used extensively as a Lewis acid in numerous organic transformations, forming adducts that mediate reactivity. Such reactions include Diels Alder, 54,355 hetero Diels Alder,356 cyclization of olefinic aldehydes,357 Flosomi Sakurai allylic coupling reactions,358 cyclopropanations,359 chal-cogen-Baylis Flillman,360 Mukaiyama Aldol reactions,36 363 reductions of ketones to alcohols 364 and stereoselective nucleophilic additions to aldehydes.365... 

Support-bound C-C-C-C fragments serve as components for cyclization in Diels-Alder and hetero-Diels-Alder reactions (HD). In normal Diels-Alder reactions these dienes should preferably be electron rich. The simplest way to introduce the diene is to couple a commercial diene or a diene synthesized by solution phase methodology to a support-bound group. This method, though efficient, restricts the user to a rather limited set of support-bound dienes. In several examples, 2,4-pentadiene-l-carboxylic acid and some of its derivatives were coupled to support-bound amines to give the support-bound diene, which is not particularly reactive in [2 -I- 4]-cycloadditions [301, 302]. 

This method was used by Hudlicky in a synthesis of the alkaloid narciclasine. The diol 90 was trapped as the usual acetal and reacted as a diene with the nitroso ester Me02C-N0 in a hetero-Diels-Alder reaction to give 91. Suzuki coupling of the vinylic bromide with the right aryl boronic acid gave 92 and the N-0 bond was reduced with Mo(CO)6 to give the advanced intermediate 93 on the way to narciclasine28 94. 

Shortly after the Sinay report, additional reports of C-disaccharide syntheses became visible. In 1984, the reported technologies included the dimerization of nitroalkanes as well as the use of hetero Diels-Alder reactions. Beginning with nitroalkane dimerizations, Vasella, et al.,2 initially studied the cross coupling of nitroalkanes and furanoside nitroglycosides discussed in section 2.6 and reviewed in Scheme 8.2.1. As demonstrated in the same report, the dimerization of furanoside nitroglycosides effectively produced C-difuranosides. The specific reaction, shown in Scheme 8.2.2, proceeded under basic conditions and the nitro group was removed on treatment with sodium sulfide. 

Reaction medium. By virtue of its attributes supercritical carbon dioxide deserves its increasing applications as a reaction medium in synthesis. These include epoxidation" with oxygen and PhCHO, rhodium-catalyzed hydroboration, Pd(0)-catalyzed 1,4-hydroarylation of enones" and Heck reaction in the presence of Pd-C," carbonylation of aryl halides, Glaser coupling of 1-alkynes (mediated by CuCy using a solid ba.se (NaOAc)," as well as seandium(III) perfluorooctanesulfonate-catalyzed Diels-Alder and hetero-Diels-Alder reaetions. ... 

Hughes et al. achieved a synthesis of amythiamicin D (121) using a biosynthesis inspired hetero Diels-Alder reaction as a key step [36]. Synthesis of the key 1-alkoxy-2-azadiene 118 was conducted by coupling of the imidate 116 and amine hydrochloride 117 and subsequent elimination of the acetate with DBU [37]. The hetero Diels-Alder reaction of the azadiene 118 and enamide 119 proceeded under microwave conditions to give the pyridine 120, which was effectively converted into the natural product 121 (Scheme 7.26). 

It has been proven that the chiral Pd(II) complexes as transition metal catalysts vs Lewis acid catalysts bring a breakthrough in the frontier of catalytic asymmetric organic synthesis. Here we discussed the key issues based on asymmetric carbon-carbon bond formations anomalous six-membered ring formation, ene-type cyclization leading to five-membered rings, spiro cycliza-tion, alkaloid and quinoline synthesis, Suzuki-Miyaura coupling, and C-H bond activation/C-C bond formation by transition metallic Pd(II) catalysts. On the other hand, the carbonyl-ene reaction, hetero Diels-Alder reaction, and... 

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