Condensation reactions convergent synthesis

Hydroxymethylation (formaldehyde) of nitro-imidazole 76 affords 77, which is oxidized to aldehyde 78. To prepare the other fragment for this convergent synthesis, reaction of epichlorohydrin with morpholine leads to the aminoepoxide 79, which is reacted with hydrazine to afford 80. Reaction of this substituted hydrazine with dimethyl carbonate affords oxazolinone 81 by sequential ester interchange reactions. Condensation of 81 with aldehyde 78 affords the antitricho-... 

Calixarenes [77] are defined as [l.n]metacyclophanes with its basic structural unit consisting of phenolic groups linked by ortho-methylene groups. Two examples are shown in Fig. 25. Several reviews are available on this subject [77-79]. These compounds can be synthesized by the acid- or base-catalyzed condensation reaction of a substituted phenol with formaldehyde or an aldehyde (Fig. 26). Calixarenes have also been synthesized by a stepwise reaction that sequentially add phenolic groups followed by a cyclization step. More efficient convergent synthesis have also been developed [80-82], The bowl-like structural conformation generally... 

Taking advantage of the Reissert approach to the synthesis of 7,8-disubstituted benzylisoquinolines, followed by Ullmann cyclization, Castedo et al. have carried out convergent synthesis of several cularine alkaloids and obtained excellent yields (48). As depicted in Scheme 4, condensation of Reissert compound 74 with benzylchlorides 78 under phase-transfer conditions and hydrolysis gives benzylisoquinolines (79). N-Methylation, reduction, and deprotection give 80, which, after Ullmann reaction, produced the following alkaloids ( )-cularine (11) from 80a (91% yield), ( )-sarcocapnine (14) from 80b (86%), and O-methyl cularicine (81) from 80c (83%). 

Celecoxib is prepared in a convergent synthesis by a classical condensation reaction, which gives a pyrazole from the corresponding 1,3-diketone and a hydrazine. [205] The hydrazine is obtained from aniline by sulfonation, diazotisa-tion and reduction. The 1,3-diketone is accessible in one step from 4-methylac-etophenone and ethyl trifluoroacetate. 

Disconnection to 62 and 60 is reasonable and suggests an enolate alkylation condensation (Chapter 22, Section 22.9). Clearly, fragment 62 is complex and will require further disconnection to obtain reasonable starting materials. This is certainly a candidate for a convergent synthesis. Disconnection to 63 and 64 is not attractive because there is little simplification. Disconnection to 65 and 66 provides simplification. Fragment 65 may be correlated with a ketone, which will react via enolate alkylation (see Chapter 22, Section 22.9). This reaction requires... 

A key step in the synthesis of the spiroketal subunit is the convergent union of intermediates 8 and 9 through an Evans asymmetric aldol reaction (see Scheme 2). Coupling of aldehyde 9 with the boron enolate derived from imide 8 through an asymmetric aldol condensation is followed by transamination with an excess of aluminum amide reagent to afford intermediate 38 in an overall yield of 85 % (see Scheme 7). During the course of the asymmetric aldol condensation... 

The number of reactions required for total biosynthesis and chemical synthesis of yersiniabactin (24) is comparable, with 22 [62] and 30 [76, 77] reactions, respectively. However, two very different strategies are used by nature and by chemists in the production of this compound. The enzymatic pathway biosynthesizes the siderophore in a linear manner, while the chemical route convergently synthesizes two molecular halves and condenses them to the final product. The number of steps required for thiazolidine formation in the chemical synthesis of... 

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