Hetero Diels-Alder reaction ring-opening

The structural diversity (and complexity) of the products obtained by the MCR between tertiary isocyano amides, aldehydes, and amines could be increased to various heterocyclic scaffolds by combining the initial 2,4,5-tiisubstituted oxazole MCR with in situ intramolecular tandem processes (Fig. 17). Most tandem processes reported are based on the reactivity of the oxazole ring toward C=C or C=C bonds in hetero Diels-Alder reactions followed by ring opening reactions generating the rather complex heterocyclic products with high degrees of variation. 

Lactam, ring formation, 288 Lactones, optically active, 31 Lanthanide complexes epoxy ring opening, 234 hetero-Diels-Alder reactions, 217 nitno-aldol reaction, 228 Laudanosine, 36 Leucine hydrocarboxylation, 168 Lewis acid complexes, 212 Ligands ... 

N-Acylimines which may react as l-oxa-3-aza-l,3-butadienes represent a class of heterodienes which exhibit a close relationship to l-thia-3-aza-l,3-butadienes [13]. A very impressive application of such an l-oxa-3-aza-l,3-butadiene has been worked out by Swindell et al.[445]. The asymmetric hetero Diels-Alder reaction described therein opens a very elegant approach to the A-ring side chain of taxol. This synthesis takes advantage of the bulky chiral auxiliary attached to the dienophile 6-5 which upon cycloaddition with the l-oxa-3-aza-1,3-butadiene 6-4 yielded the 1,3-oxazine derivative 6-6. Subsequent hydrolysis, hydrogenolysis and transesterification gave the methyl ester of the taxol A-ring side chain 6-7 in good endo and excellent zr-facial selectivity (Fig. 6-2). 

The mesomeric betaine (100) underwent 1,3-dipolar cycloaddition, with DMAD in toluene at 100°C, to give a mixture of two products (101) and (102). Compound (101) was formed by initial 1,3-dipolar cycloaddition of DMAD to the azomethine ylid fragment of (100) to yield a tricyclic intermediate which fragmented to (101). Compound (102) was formed via ring opening of (100) to a ketene intermediate which underwent a hetero Diels-Alder reaction with DMAD to give (102) <92JCS(P1)2789>. 

Some of the important click reactions are (Kolb and Sharpless 2003 Adzima and Bowman 2012) azide-alkyne azide-sulfonyl cyanide benzyne-azide cycloaddition and hetero Diels-Alder reactions nucleophilic ring opening of strained molecules such as epoxides, aziridines, etc. non-aldol-type reactions and additions to carbon-carbon multiple bonds through oxidation-type reactions such as epoxidation, hydrox-ylation, etc. For more details, the reader is referred to a recent review by Adzima and Bowman (2012). 

A SALEN-containing catalyst, A,A-bis(3,5-di-tert-butylsalicylidene)-l,2-cyclohexanediamino-cobalt(II), proved to be an efficient catalyst for the hydrolytic kinetic resolution of terminal epoxides (187) and the enantioselective ring opening of meso epoxides (188). The same complex proved to be active in the asymmetric hetero-Diels-Alder reaction (189). 

The first total synthesis of the cytotoxic agent (+)-euplotin A was completed by the research team of R.L. Funk. The key step of the synthetic effort was the intramolecular hetero DIels-Alder cycloadditlon of a 3-acyl oxadiene (generated from 5-acyl-4H-1,3-dioxins via thermal retrocycloaddition) with a substituted dihydrofuran to afford the tricyclic skeleton of the natural product. The correct relative stereochemistry of the required dihydrofuran substrate was established using the Paterno-Buchi reaction between ethyl glyoxylate and furan. Subsequently, the oxetane ring was opened stereoselectively under Lewis acid catalysis. 

Cocyclotrimerization, if applied to 1,5-hexadiynes 7, leads to benzocyclobutenes 8. After smooth thermal ring opening, these give highly reactive ort/io-quinodimethanes 9, which can be trapped by Diels-Alder reaction with an alkene or hetero-carbon multiple bond. If these dienophiles are in a side chain of the primary diync, the conversion leads in a one-pot version to carbo- and heterocyclic polycyclic systems with defined trans stereochemistry at the newly... 

High-pressure organic synthesis (including hetero Diels-Alder and 1,3-dipolar [3 + 2] cycloaddition reactions and epoxide ring opening) 05Y770. 

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