Domino reactions sequence

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. 

Wittig yhdes have been shown to be compatible with hydroformylation conditions, and may thus be used in a domino reaction sequence such as from 16a to 38 (Scheme 5.15) [20]. When an a-unsubstituted ylide is employed, the resulting alkene undergoes in-situ rhodium-catalyzed hydrogenation in a triple tandem reaction to convert 10 a to 39. Several other examples were reported establishing the generality of this domino reaction sequence. 

A gold(I)-catalyzed domino reaction sequence involving pentenynyl tosylamides led to the formation of 2,3-disubstituted pyrroles containing a quaternary center in the 2-substituent <07OL3181>. The mechanism of the reaction involved a 5-endo-dig cyclization followed by an aza-Claisen rearrangement. 

Breit, B. Controlling Stereoselectivity with the Aid of a Reagent-Directing Group. Hydroformylation, Cuprate Addition, and Domino Reaction Sequences, Chem. Eur. J. 2000,1519-1524. 

The ability of L-Pro to promote the Knoevenagel reaction has been harnessed in domino reaction sequences for the preparation of important target products. Several bicyclic and polycyclic systems have been obtained by these means. As an example, coumarines were prepared by the one-pot condensation reaction of o-hydroxybenzaldehydes with active methylene compounds (Scheme 2.8). In a related procedure, flavanones were synthesised from aromatic (3-ketoesters and aldehydes (Scheme 2.8). The domino sequence comprises in this case, a proline-catalysed Knoevenagel condensation and an intramolecular Michael addition. 

Diversity and molecular complexity are two important criteria that emich a compound collection in biological activity [48, 49). Therefore, strategies that efficiently build up diverse and relatively complex molecular architectures, in particular based on natural product frameworks, are highly desired. Branching pathways in DOS pose formidable challenge of incorporating scaffold diversity in a compound collection. Cascade or domino reaction sequences [50, 51] wherein more than one reaction happens consecutively in a one-pot strategy and molecular complexity is rapidly built up can immensely improve the efficiency of diversity syntheses endeavors (Box 27.3). Kumar and coworkers introduced a... 

The potency of Danheiser s pericyclic cascade was further demonstrated in the construction of pyridine cores, disclosing presumably the first example in which an unactivated nitrile function participates in a [4+2]-cycloaddition. Two examples with established mechanisms are depicted in Scheme 6.33. If the required hydrogen for the anticipated ene reaction is present, pathway A dominates and follows the common domino reaction sequence to pyridine 181. If, however, the crucial position is substituted, for instance by an amide moiety, the system is able to overcome this hurdle and utilize its nitrile group for the preluding ene reaction (pathway B). This time, the alkyne group eventually terminates the cascade in a cycloaddition to give the tricyclic pyridine 184. Some efforts has been made to prove that pathway A is usually faster a gem-dialkyl effect in the substrates 179 as well as 182 was shown to play a role in order to facilitate the reaction progress. 

Briere and coworkers gained rapid access to the pyrazolines ring system 300 through a Michael-based domino reaction sequence. This enantioselective process... 

In contrast to the total synthesis of an NP, which often is a long, multistep, and time-consuming endeavor, generating NP-like compounds should follow easy and efficient synthesis routes to provide a large number of compounds. Domino reaction sequences can play a major role in providing relatively complex and NP-based compound collections. ChiraHty of the product is another important factor that determines the biological effect of a molecule. Therefore, enantioselective and diastereoselective domino reactions are of particular interest in this area. 

This strategy led to the synthesis of a small compound Hbrary of indoloiso-quinolines with functional group variations on the aromatic rings and with yields between 42 and 95%. Furthermore, a concise synthesis of the NPs themselves was achieved by employing this domino reaction sequence as a key transformation. Pentacyclic substrate 9 was obtained through the silver-catalyzed domino polycy-clization between acetylenic indole-2-carbaldehyde 7 and anihne 8. Pentacycle 9 was subsequently transformed into homofascaplysin C (10) in only one formylation step (overall yield of 54%), while two further transformations provided fascaplysin (11) in overall yield of 52% (Scheme 13.2). 

The particularly mild conditions of Passerini reactions, and the corresponding broad functional group tolerance, has meant that many reactive functionalities can remain unprotected on the component substrates and then utilized in a secondary reaction as a tandem or domino reaction sequence. Notably, this facet has led to the extensive use of the Passerini reaction for the construction of numerous functionalized furans, oxazoles, tetrazoles, P-lactams, butenolides and other complex heterocycles. 

Fig. 17) [57]. The use of this outstanding DIB-mediated phenol dearomatization/ Pd-catalyzed domino reaction sequence was then also further extended to build polycyclic benzofurans [57]. Fan had also earlier described a related method using the same initial DIB-mediated phenol dearomatization tactic in the presence of indole nucleophiles and an Ag(I) catalyst to prepare 4-indolylbenzofurans from 4-aUcyl-2-aIk ynylphenols [58]. 

Under ruthenium-catalyzed ortho-C-H activation and intramolecular C-N bond formation, the condensation of iminophosphoranes (in situ generated from acyl azides and triphenylphosphine) with internal alkynes afforded a variety of isoquinolinone derivatives (Eq. (7.43)) [53]. The regioselective insertion of unsymmetrical alkynes led to an (aryl)C-N bond formation. Thiophene and indole-based acyl azides were also compatible for this transformation. A domino reaction sequence via coordination of ruthenium with Af-atom of iminophosphoranes, ort/zo-cyclometalation, alkyne insertion, protonation, and reductive elimination was proposed for the catalytic cycle. Based on and NMR experiments, the involvement of benzamide during the reaction process was ruled out. 

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