One-pot transformation

The coupling of enals and glyoxals was realized by hydrogen-mediated reaction with the cationic Rh complex and PI13P [35]. The intermediate aldehyde enolates derived via Rh-catalyzed hydrogenation were trapped with glyoxals to form (l-hydroxy-y-kclo-aldchydes, which were treated sequentially with hydrazine to give pyridazines in a one-pot transformation to provide, for example, a 62% yield of 72 (Scheme 21). 

One Pot Transformation of Geraniol into Citronellol and Menthol over Cu/A1203... 

A similar reaction (which is not a domino process in its strict definition but a useful one-pot transformation) was described by Queiroz and coworkers [116]. Reaction of bromobenzothiophene 6/1-233 with pinacolborane in the presence of Pd(OAc)2 and a phosphine followed by addition of 2-bromonitrostyrene 6/1-234 led to 6/1-235, normally in good yields (Scheme 6/1.60). 

Diels Alder (DA) and 1,3-dipolar cycloaddition (1,3-DC) reactions are simple and very versatile transformations to introduce a wide range of substituents at the meso- and beta-pyrrolic positions of porphyrins, thus leading to promising derivatives obtained in many cases in one-pot transformations. 

The preparation of 2,3,5-trisubstituted 4,5-dihydrofurans 81 with complete regio-control can be realized by an one-pot transformation involving epoxidation of 2-alkenyl-1,3-dicarbonyls by in situ generated dimethyldioxirane, and is followed by a S-exo-ieX intramolecular nucleophilic cyclization under the same basic condition <00TL10127>. 

As these reagent systems are anchored on a solid, they also allow the simultaneous use of multiple reagents to achieve one-pot transformations where, because of incompatibility of the reagents, no solution-phase equivalent exists or would require intermediate isolation. Many examples of this are illustrated in the following sections where it can be seen that these concepts add a new dimension to how one can think about organic synthesis and will certainly have important ramifications on the design and implementation of new chemical reactions and processes in the future. 

An interesting entry to functionalized dihydropyrans has been intensively studied by Tietze in the 1990s using a three-component domino-Knoevenagel Hetero-Diels-Alder sequence. The overall transformation involves the transient formation of an activated heterodienophile by condensation of simple aldehydes with 1,3-dicarbonyls such as barbituric acids [127], Meldrum s acid [128], or activated carbonyls. In situ cycloaddition with electron-rich alkenes furnished the expected functionalized dihydropyrans. Two recent examples concern the reactivity of 1,4-benzoquinones and pyrazolones as 1,3-dicarbonyl equivalents under microwave irradiation. In the first case, a new three-component catalyst-free efficient one-pot transformation was proposed for the synthesis of pyrano-1,4-benzoquinone scaffolds [129]. In this synthetic method, 2,5-dihydroxy-3-undecyl-1,4-benzoquinone, paraformaldehyde, and alkenes were suspended in ethanol and placed under microwave irradiations to lead regioselectively the corresponding pyrano-l,4-benzoquinone derivatives (Scheme 38). The total regioselectivity was... 

Over the past 15 years, we developed three procedures for the iron-mediated carbazole synthesis, which differ in the mode of oxidative cyclization arylamine cyclization, quinone imine cyclization, and oxidative cyclization by air (8,10,557,558). The one-pot transformation of the arylamine-substituted tricarbonyl(ri -cyclohexadiene) iron complexes 571 to the 9H-carbazoles 573 proceeds via a sequence of cyclization, aromatization, and demetalation. This iron-mediated arylamine cyclization has been widely applied to the total synthesis of a broad range of 1-oxygenated, 3-oxygenated, and 3,4-dioxygenated carbazole alkaloids (Scheme 5.24). 

An attempt to directly convert hyellazole (245) to 6-chlorohyellazole (246) by reaction with N-chlorosuccinimide in the presence of a catalytic amount of hydrochloric acid led exclusively to 4-chlorohyellazole. On the other hand, bromination of 245 using NBS and a catalytic amount of hydrobromic acid gave only the expected 6-bromohyellazole (733). Alternatively, a direct one-pot transformation of the iron complex 725 to 6-bromohyellazole (733) was achieved by reaction with an excess of NBS and switching from oxidative cyclization conditions (basic reaction medium) to electrophilic substitution conditions (acidic reaction medium). Finally, a halogen exchange reaction with 4 equivalents of cuprous chloride in N,N-dimethylformamide (DMF) at reflux, transformed 6-bromohyellazole (733) into 6-chlorohyellazole (246) (602) (Scheme 5.73). 

The arylamine 780b required for the total synthesis of carbazomycin B (261) was obtained by catalytic hydrogenation, using 10% palladium on activated carbon, of the nitroaryl derivative 784 which was obtained in six steps and 33% overall yield starting from 2,3-dimethylphenol 781 (see Scheme 5.85). Electrophilic substitution of the arylamine 780b with the iron-complex salt 602 provided the iron complex 787 in quantitative yield. The direct, one-pot transformation of the iron complex 787 to carbazomycin B 261 by an iron-mediated arylamine cyclization was unsuccessful, probably because the unprotected hydroxyarylamine moiety is too sensitive towards the oxidizing reaction conditions. However, the corresponding 0-acetyl derivative... 

An alternative approach was used in the synthesis of the herbicide 530, where the sulfoxide 529 was converted to 530 in a single step by heating with lithium chloride in refluxing pyridine <1997TL4339>. The one-pot transformation involves sigmatropic sulfoxide elimination, lithium chloride-induced demethylation of the carbomethoxy group, decarboxylation, and a final isomerization/aromatization step <1997TL4339>. 

Aliphatic and aromatic carboxylic esters are also directly converted, in one step, to oxazolines using amino alcohols. As expected, harsh conditions are required for this transformation. Typically, the reaction is performed in refluxing xylene in the presence of catalytic quantities of a Lewis acid such as dibromo- " or dichloro-dimethylstannane. More recently, lanthanide chloride and samarium chloride have also been reported as useful catalysts for this one-pot transformation in refluxing toluene. Representative examples are shown in Table 8.2 (Scheme 8.2). ... 

The Grignard route is better it is a one-pot transformation. Converting the secondary bromide to a nitrile will be accompanied by elimination, and the procedure requires two separate operations. 

ONE-POT TRANSFORMATIONS INVOLVING SUCCESSIVE HYDROGENATION AND ACID-BASE STEPS... 

Although in most cases reaction conditions for these one-pot-transformations are rather harsh, it is conceivable that optimization might lead to milder methods in singular cases. Nevertheless, these straightforward transformations make available a variety of interesting products by very simple and cheap procedures. 

A more general approach to cyclopropanes from allylic ethers has recently been reported [28]. Two steps are involved in this one-pot transformation, i.e., hydrozirconation reaction followed by Lewis acid-promoted deoxygenative ring formation. The overall transformation is symbolized in Scheme 21, Eq. 1,... 

---