Domino reactions aldehydes

The hydroformylation reaction strategy has recently been extended, in a novel way, to the manufacture of primary amines by hydroaminomethylation of olefins with ammonia in a two-phase system. Thus, 1-pentene was reacted with ammonia here hydroformylation to an aldehyde, with CO and H2, with subsequent reductive amination occurs in a domino reaction. The catalyst was Rh/Ir/TPPS (Zimmermann et al., 1999). 

The combination of a Corey-Kwiatkowski [147] and a HWE reaction efficiently furnishes a, 3-unsaturated ketones of type 2-288 in good yields [148]. This unique domino reaction, developed by Mulzer and coworkers, probably proceeds via the intermediates 2-285 and 2-286 using the phosphonate 2-283, the ester 2-284, and the aldehyde 2-286 as substrates (Scheme 2.66). 

It has been assumed that formation of the cis-fused product 2-771 in the domino reaction of aldehyde 2-769 is due to a strongly favored exo-Z-syn transition state 2-770. The endo-E-syn structure is prohibited by the rigidity of the acetonide existing in 2-769, whereas the proximity of the same moiety to the benzyloxymethyl substituent at the double bond disfavors the exo-E-anti transition state, which would be responsible for the formation of the trans-fused diastereomer. 

An earlier example of this type of domino reaction was reported by Greeves and coworkers (Scheme 2.194) [443]. Treatment of either the ( )- or (Z)- allyl vinyl ether 2-870 with NaH initiates the [2,3]-Wittig rearrangement to afford 2-872 via 2-871. The subsequent oxy-Cope rearrangement led to the aldehyde 2-873, which was reduced with NaBH4 to give the alcohols 2-874. Both isomers of 2-870 predominantly generated the (/ )-xyu-product 2-874 in comparable ratios as the main product. 

In 1987, Vaultier and coworkers [27] developed a combination of a [4+2] cycloaddition of a bora-1,3-diene to provide an allylborane, which then reacts with an aldehyde to give a highly functionalized alcohol. The Lallemand group, as well as Hall and colleagues, has recently used this procedure. In an approach for the synthesis of the antifeedant natural product clerodin (4-83), Lallemand and coworkers performed a three-component domino reaction of 4-80, 4-81 and methyl acrylate to give 4-82 (Scheme 4.18) [28]. 

The Hall group [52] has developed a new three-component domino reaction of 1-aza-4-borono-1,3-butadiene 4-152, a dienophile and an aldehyde to give a-hydroxy-methylpiperidine derivatives. In the first step, a hetero-Diels-Alder reaction takes place, which is followed by allylboration. As an example, reaction of 4-152 with the maleimide 4-153 in the presence of benzaldehyde furnished 4-154 in yields of up to 80% using the three substrates in a 1 2 1 ratio (Scheme 4.32). 

In a similar way, Carreaux and coworkers [53] used 1-oxa-l,3-butadienes 4-155 carrying a boronic acid ester moiety as heterodienes [54], enol ethers and saturated as well as aromatic aldehydes. Thus, reaction of 4-155 and ethyl vinyl ether was carried out for 24 h in the presence of catalytic amounts of the Lewis acid Yb(fod)3 (Scheme 4.33). Without work-up, the mixture was treated with an excess of an aldehyde 4-156 to give the desired a-hydroxyalkyl dihydropyran 4-157. Although this is not a domino reaction, it is nonetheless a simple and useful one-pot procedure. 

N-Acyl-a-amino acids are important compounds in both chemistry and biology. They are easily obtained in a transition metal-catalyzed, three-component domino reaction of an aldehyde, an amide, and CO. Whereas cobalt was mainly used for this process, Beller and coworkers [159] have recently shown that palladium has a... 

During the past few years, increasing numbers of reports have been published on the subject of domino reactions initiated by oxidation or reduction processes. This was in stark contrast to the period before our first comprehensive review of this topic was published in 1993 [1], when the use of this type of transformation was indeed rare. The benefits of employing oxidation or reduction processes in domino sequences are clear, as they offer easy access to reactive functionalities such as nucleophiles (e. g., alcohols and amines) or electrophiles (e. g., aldehydes or ketones), with their ability to participate in further reactions. For that reason, apart from combinations with photochemically induced, transition metal-catalyzed and enzymatically induced processes, all other possible constellations have been embedded in the concept of domino synthesis. 

Today, multi-parallel synthesis lies at the forefront of organic and medicinal chemistry, and plays a major role in lead discovery and lead optimization programs in the pharmaceutical industry. The first solid-phase domino reactions were developed by Tietze and coworkers [6] using a domino Knoevenagel/hetero-Diels-Alder and a domino Knoevenagel/ene protocol. Reaction of solid-phase bound 1,3-dicarbonyl compounds such as 10-22 with aldehydes and enol ethers in the presence of piperidinium acetate led to the 1-oxa-1,3-butadiene 10-23, which underwent an intermolecular hetero-Diels-Alder reaction with the enol ethers to give the resin-bound products 10-24. Solvolysis with NaOMe afforded the desired dihydro-pyranes, 10-25 with over 90 % purity. Ene reactions have also been performed in a similar manner [7]. 

Several multi-component domino reactions for the preparation of libraries have been developed in the last years.141 One of the first examples in solution is a four-component reaction described by Ugi et al. in which a carbocyclic acid 5, an aldehyde 6 and an isocyanide 7 are condensed in presence of methanol to give amino acids 8 (scheme 2).151... 

Domino reactions increasingly gain importance in the search for new drugs. Especially appropriate is the use of multi-component reactions in solution combinatorial chemistry. In such a process described by Wessel et al.1231 an alkoxy-nitroenone 48 was treated with different anilines 49 to give ketene-NO-acetals which in the presence of aromatic aldehydes and TfOH are transformed into 50 (scheme 10). The substrate 48 is readily available by oxidation of the nitrosugar 47. 

Hydroformylation reactions have been shown to be amenable to use in tandem or domino reaction sequences. In one elegant example, alkene 36 was subjected to rho-dium(I)-catalyzed hydroformylation, and the resulting aldehyde underwent smooth intramolecular allylboration (Scheme 5.14) [19]. This produced a new terminal alkene which underwent a second hydroformylation to provide, after workup,lactols 37 in 80% yield and with excellent diastereoselectivity. 

Abstract The purpose of this chapter is to present a survey of the organometallic chemistry and catalysis of rhodium and iridium related to the oxidation of organic substrates that has been developed over the last 5 years, placing special emphasis on reactions or processes involving environmentally friendly oxidants. Iridium-based catalysts appear to be promising candidates for the oxidation of alcohols to aldehydes/ketones as products or as intermediates for heterocyclic compounds or domino reactions. Rhodium complexes seem to be more appropriate for the oxygenation of alkenes. In addition to catalytic allylic and benzylic oxidation of alkenes, recent advances in vinylic oxygenations have been focused on stoichiometric reactions. This review offers an overview of these reactions... 

The asymmetric domino reactions between 2-mercaptobenzaldehyde and a,fi-unsaturated aldehydes proceed with excellent chemo- and enantio-selectivities in the presence of (99) (20 mol%) as organocatalyst to afford 2//-l-benzothiopyrans (98) in high yields with 91-98% ee.145... 

Scheme 5.46. Domino reaction of aniline 234 with aldehyde 233.

Scheme 5.47. Domino-reaction of aminothiadiazole 238 with aldehyde 237.

List and Castello discovered a proline-catalyzed three-component domino reaction between ketones, aldehydes, and Meldrum s acid forming corresponding ketoesters (Scheme 9.19) [30],... 

The first step of this domino reaction opens the lactone 15 by reaction with potassium carbonate in methanol leading to hemiacetal 49. This is not stable under the reaction conditions and decomposes yielding aldehyde 50 and PMBOH 35 (see formation of acetal 40 described above). 

One may improve efficiency of an o-DPPB directed hydroformylation by incorporating this reaction into sequential transformations (domino reactions) [16]. The hydroformylation itself should be ideally suited for such a purpose, since this reaction provides under fairly mild reaction conditions access to the synthetically valuable aldehyde functionality. The aldehyde itself should be ideally suited to allow for further skeleton-constructing reactions. One type of sequential transformations employing the hydroformylation reaction as a key step is the hydroaminomethylation of olefins originally discovered by Reppe [17]. However, efficient control of diastereoselectivity in the course of this hydroaminomethylation reaction was unknown [18, 19]. 

The asymmetric domino reaction between 2-mercaptobenzaldehyde and a,f)-unsaturated aldehydes proceeds with excellent chemo- and enantio-selectivities to afford 2-substituted 3-formyl-2//-l bcnzothiopyrans, products of a formal Baylis-Hillman reaction, when the. 9-proline derived catalyst 407 is employed (Scheme 123) <2006TL8547>. 

The domino reaction consists of a Knoevenagel condensation giving an intermediate that immediately undergoes an intramolecular hetero-Diels-Alder reaction with inverse electron demand [31]. As aldehydes, rac-dtronellal, an aromatic aldehyde, and two commercially available 1,3-diketones, 1,3-dimethylbarbituric add and Meldrum s acid, were seleded. By combinations of these reactants, different cycloadducts were generated. 

Marigo M, Schulte T, Franzen J, Jprgensen KA (2005b) Asymmetric multicomponent domino reactions and highly enantio selective conjugated addition of thiols to alpha,beta-unsaturated aldehydes. J Am Chem Soc 127 15710-15711... 

Cook and co-workers have described a Pd-catalyzed domino reaction for the preparation of the quinuclidine subunit common to a variety of alkaloids, e.g., 146 to 147 <07OL1469>. In a separate report from the same group, enantiospecific total synthesis of 6-epi-vellosimine 148 proceeded with judicious use of the Corey-Kim reagent (NCS/N S/CH Ch EtsN) for mild access to the delicate axial aldehyde of 148 from the corresponding alcohol <07OL295>. 

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