Three-component process

In a recent publication, Perumal and coworkers [441] described the condensation of an aldehyde 2-863 with an aniline 2-864 to give an imine which is trapped by a dienophile. However, when using this approach an intermolecular cycloaddition takes place as the reaction is performed as a three-component process using enol ethers or cyclopentadiene as dienophiles (Scheme 2.192). When using enol ether 2-... 

The de Meijere group [63] prepared interesting spiro-compounds containing a cyclopropyl moiety using a combination of a Heck and a Diels-Alder reaction, with bicyclopropylidene 6/1-115 as the starting material. The transformation can be performed as a three-component process. Thus, reaction of 6/1-115, iodobenzene and acrylate gave 6/1-116 in excellent yield. With vinyliodide, the tricyclic compound 6/1-117 was obtained (Scheme 6/1.31). Several other examples were also described. 

Typically, pyridinium salts are prepared through reaction of an intact pyridine with electrophiles. Marazano el al. used a three-component process as entry into 3-substituted pyridinium salts for the preparation of 49 as shown below <06TL5503>. 

Elegant contributions to this fidd have also been made by Grigg et al espedally interesting are his palladium-anion capture domino processes. By this way a direct route to protected pseudoargiopinine III 127, a toxine from Argiope bbata, has been developed using a three-component process of allene 125... 

In another three-component process, 1-chlorovinyl p-tolylsulfoxidcs 181 are first prepared from ketones (Scheme 5.27) [71]. 

N-Substituted 4-methylene-3,4-dihydro-l-(2H)-isoquinolin-l-ones are synthesized by means of a palladium-catalyzed three-component process (Scheme 16.5) [9]. 

In order to testify to the versatility of the Reformatsky reaction, two examples of three-component processes are presented the synthesis of 3-aryl-4,4-dimethyl-2-oxaspiro[5.5] undecane-1,5-diones 1485 (equation 12), and the coupling of two molecules of methyl 2-bromo-2-methyl propanoate (If) with an oxoaryl acetaldehyde 15 to afford 3a-aryl-3,3,6,6-tetramethyl-tetrahydrofuro[3,2-b]furan-2,5-dione 1686 (equation 13). 

Many elegant reactions that exploit such nickel-catalyzed three-component processes have been described59,60 and some representative examples will be indicated. 

The Zr-catalyzed asymmetric alkylation shown in Eq. (2) [8] illustrates two important principles (1) The catalytic asymmetric protocol can be readily applied to the synthesis of non-aryl imines to generate homochiral amines that cannot be prepared by any of the alternative imine or enamine hydrogenation protocols. (2) The catalytic amine synthesis involves a three-component process that includes the in situ formation of the imine substrate, followed by its asymmetric alkylation. This strategy can also be readily applied to the preparation of arylamines. The three-component enantioselective amine synthesis suggests that such a procedure maybe used to synthesize libraries of homochiral amines in a highly efficient and convenient fashion. 

While the above stepwise bimolecular process was well suited for reactions with paraformaldehyde, other aldehydes and ketones did not behave similarly, presumably because of incomplete reactions between the amine and the carbonyl components. To overcome these difficulties, we invented a three-component process (Scheme 7.6) based on the one-step reaction between various amines 38, carbonyls 39, and boronic acids or boronates 40 to give the corresponding amine derivatives... 

The use of diamine derivatives in the three-component process leads to peptidomimetic heterocycles, such as 2-oxopiperazines (piperazinones) [58], benzopiperazi-nones [58] and benzodiazepines. In fact, the 2-oxopiperazines 89 can be obtained directly in one step via the reaction of a diamine 85 with glyoxylic acid 86 and a boronic acid 87 (Scheme 7.12) [58]. Presumably, the intermediate amino acids 88 can undergo a subsequent boronic acid-catalyzed lactamization [29] to afford 89. A two-step approach was used for the synthesis of benzopiperazinones (e.g. 96) [58]. 

The one-step three-component process among amines, boronic acids and sali-cylaldehydes 140 gives the corresponding aminomethylphenol derivatives 143 (Scheme 7.19) [65], presumably via the intramolecular reaction among the imi-nium borate species, as illustrated in 142. 

Pyridylaldehydes 161 [67] and other similar heterocyclic aldehydes [68] also participate in the three-component process affording aminomethylpyridine derivatives 163 (Scheme 7.21). This process can be used to generate novel molecules, such as 166, that contain three different heterocydes, each of which is introduced via one of the three components. 

An unusual variation of the three-component process involves the use of unprotected carbohydrates 201, nature s chiral a-hydroxy aldehydes, as the carbonyl com-... 

In the context of a coupling-1,3-dipolar cycloaddition sequence, Muller and coworkers [89] developed a consecutive one-pot, three-component process to indolizines. Starting from (hetero)arenecarbonyl chlorides 88 and terminal alkynes 89 under Sonogashira conditions, the expected alkynones were formed (Scheme... 

A diastereoselective three-component process to prepare 2//-pyrimido[2,1 -a]-isoquinolines 84 from isoquinoline was reported <01OL3575>. Pyrrolo[2,l-a]isoquinolines were also prepared by an annelation reaction with l,l-diiodo-2,2-dinitroethylene and isoquinolinium salts containing active methylene groups <02SL1547>. 

In 1990, Xia and Kozikowski improved the preparation of key intermediate 4 from 3 (Scheme 4-3). They used an efficient one-pot, three-component process to prepare 2-pyridone 6 from a carbonyl compound, ammonia, and methyl propio-late, which enhanced the yield of 2a and avoided those expensive reagents. In 1993,... 

Sheibani H, Saljoogi AS, Bazgir A (2008) Three-component process for the synthesis of... 

We used a new silane which readily permits quantitative conversion of silanol-terminated fluids into aminopropyl-terminated fluids. The reaction between aminopropyl-terminated fluids and diisocyanates proceeds smoothly within a few minutes, either in solution or in the melt. The preparation of siloxane-urea block copolymers is performed in either a two- or a three-component process. By carefully choosing the inorganic segment defined by the corresponding silicone fluid, it is possible to obtain silicone mbbers with different material characteristics. The mechanical properties can be tuned from very soft to very hard. Those materials display tensile strengths up to 14 MPa without requiring additional fillers and can be used for diverse applications. 

A simple, clean, and environmentally benign three-component process to the synthesis of 2-amino-4H-chromenes using A,A-dimethyl aminoethylbenzyldimeth-ylammoniumchloride, [PhCH MejN CHjCHjNMeJCl, as an efficient catalyst under solvent-free condition was reported by Chen et al. (Fig. 12.75) [45],... 

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