RCM/oxidation

Nan and coworkers employed an RCM/oxidation strategy for the synthesis of aromatic 2-pyridones from acrylamides 50. Treating acrylamides 50 with Grubbs second-generation catalyst 3 followed by subsequent oxidation of the dihydropyridone intermediate with 2,3-dichloro-5,6-dicyano-l,4-ben-zoquinone (DDQ) resulted in the synthesis of 3-amino-2-pyridones 51. This methodology was tolerant of a variety of substituents at the 6-position and the resulting pyridones were obtained in moderate to good yields. As shown in Scheme 15, the substituents at the 6-position include aliphatic. 

After RCM, oxidation of cyclized products that lack a degree of unsaturation of aromatization is a simple and powerful method as well as the above-mentioned direct method for the synthesis of aromatic compounds. Although aromatic compounds by an RCM/oxidation sequence in early examples had been considered to be undesirable products, many researchers now use this sequence intentionally for the synthesis of various aromatic compounds. For example, the formation of tetracycle... 

Scheme 26.12 shows examples of the synthesis of pyrroles. Dieltiens et al. obtained pyrroles 43 by an RCM/oxidation sequence of diallyamines 42 in which Grubbs s second-generation catalyst 2 and chloranil (44) were used simultaneously [19]. At first, Dieltiens et al. used an RuCls catalyst system for the oxidation [19b]. However, there was a modification to use chloranil (44) because of the slow reaction rate of the RuCb catalyst system. 

Another way to reduce the nucleophilicity of the sulfur atom is oxidation to the corresponding sulfones, sulfonamides or sultones. Thus, diallyl sulfone undergoes RCM to the corresponding sulfolene smoothly in the presence of... 

In a more recent and improved approach to cyclopropa-radicicol (228) [ 110], also outlined in Scheme 48, the synthesis was achieved via ynolide 231 which was transformed to the stable cobalt complex 232. RCM of 232 mediated by catalyst C led to cyclization product 233 as a 2 1 mixture of isomers in 57% yield. Oxidative removal of cobalt from this mixture followed by cycloaddition of the resulting cycloalkyne 234 with the cyclic diene 235 led to the benzofused macrolactone 236, which was converted to cyclopropa-radicicol (228). 

Next step is the construction of 8- and 15-membered ring systems by sequential RCM [7]. Tetracyclic alcohol 13 was converted to 14 by sequential oxidation and Peterson olefination followed by deprotection of the TMS group. After protection of the amine with a Boc group, the imide carbonyl group was... 

When large rings are constructed by RCM, 2JE- somer c mixtures can result. Hence RCM-based macrocyclizations are best suited for the preparation of intermediates in which the C-C double bond formed by metathesis can be removed (by, e.g., hydrogenation or oxidation) at a later stage of the synthesis. 

Compounds in this class are usually made from specific precursors with the ultimate functionalities appearing in the starting materials. Syntheses in which one new bond is formed (cyclizations) usually involve substitution or condensation reactions. Two new closures with potentially some generality have been noted in this chapter. One of the intramolecular Diels-Alder reactions (see Section 13.12.8.1) and the other RCM (see Section 13.12.8.1). The Baeyer-Villiger reaction is still very much used for the preparation of lactones. A supported catalyst and a recyclable catalyst carried in an ionic liquid have been introduced for use in Baeyer-Villiger oxidations from other areas. 

On the other hand, 65 (R=MOM), obtained through 63-65 (R=MOM) by employing the same sequence involving RCM, was converted into 66 on sequential diastereoselective epoxidation, protection and oxidation. On treatment with DBU, 66 afforded 67 serving as the precursor of (-)-shikimic acid (Scheme 18).26... 

Thiochromen 4-yl enol phosphates have been obtained from 2 -fluoroacetophenone through initial reaction with prop-2-enethiol followed by conversion to the enol phosphate. Ring closing metathesis (RCM) using a second generation Grubbs catalyst delivered the. V-hctcrocycle. Oxidation at sulfur prior to RCM provided access to the thiochromen-4-yl 1,1-dioxide enol phosphate (Scheme 120) <2003TL4275>. 

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