One-pot three-component coupling

Jprgensen has also developed a one-pot three component coupling of 1,3-dicarbonyl compounds, a,P-unsaturated aldehydes and primary amines to give a series of Hantzsch ester analogues [99],... 

Scheme 5.20 One-pot, three-component coupling-1,3-dipolar cycloaddition synthesis of indolizines.

The Garner group has developed a silver acetate/triphenylphosphine (10mol%) catalyzed one-pot three-component coupling (Scheme 2.20) of aldehydes 72, methyl acrylate (27), and dimethyl-2-aminomalonate (73,2 equiv).39 Notably, both aliphatic and aromatic aldehydes may participate in the reaction and yields up to 95% can be achieved. 

The ruthenium-catalyzed olefin cross-metathesis to the preparation of functionalized allyl boronates has resulted in a one-pot three-component coupling procedure for the synthesis of functionalized homoallylic alcohols.617,618 The utility of the protocol was demonstrated in asymmetric allylboration using a tartrate ester (Equation (152)).617... 

The scope of the Cu-catalyzed cycloaddition between propargylamines and electron-deficient olefins in the presence of catalytic amounts of a copper salt was subsequently expanded to a one-pot, three-component coupling strategy involving phenols as third components [65]. In this case, reactive Michael acceptors such as ethyl 2-aryl- or alkylsulfonyl cinnamates 57 are involved in the process. This sequence leading to 3(4)-phenoxymethyl pyrrolidines 60 and their isomeric pyrrolidines 61 comprises of the relay process of... 

A related one-pot three component coupling reaction leading to allyli-dene tetrahydrofuran derivatives 80 and which combines a conjugate addition of a propargyl alcohol with an activated olefin and an in situ palladium-catalyzed carbopalladation-cyclization in the presence of a large excess of allyl chloride has been recently developed by Lu and Iiu (Scheme 31) [77]. The cyclization process is here initiated by addition of a catalytic amount of Pd(OAc)2 and in marked contrast with the above-discussed reactions, a catalytic cycle involving divalent palladium proceeds in the reaction. In this process, the ester enolate formed in the Michael addition undergoes... 

The key element of this protocol is the initial addition of cationic electrophiles such as rerr-alkyl or acyl cations to the double bond of a DCHC complex of the conjugated enyne 118, which results in the formation of the substituted propargylic cation intermediate 119, Subsequent reaction with pre-selected external nucleophiles, for example allylsilanes or silyl enol ethers, leads to the formation of the final adducts 120. The reaction is carried out as a one-pot, three-component coupling and can be used for the creation of two novel C-C bonds. It is a process somewhat complementary to the stepwise Michael addition described earlier (Scheme 2.31), with a reverse order of E and Nu addition. Oxidative decomplexation of 120 yields the product 121. The overall... 

Catalysed by CS2CO3 and TBAI a mild and efficient one pot three component coupling was performed using dialkylphosphite, CS2 and alkyl halide leading to phosphonodithioformates (312) (Scheme 82). ... 

The reaction of an N-acyliminium ion pool with an alkene or alkyne followed by trapping of the resulting carbocation by water leads to the formation of the corresponding carbohydroxylation product. Cationic sequential one-pot, three-component coupling reactions of an N-acyliminium ion can also be accomplished using an electron-rich olefin and a suitable nucleophile that traps the thus-generated cationic intermediate as shown in Scheme 5.17. ... 

Scheme 5.17 Sequential one-pot, three-component coupling of an N-acyliminum ion pool...

Trifluoroethanol is an efficient and recyclable solvent in helping one-pot, three-component coupling reactions of aldehydes or ketones, amines, and trimethyl-silyl cyanide or trimethyl phosphate to yield the corresponding a-amino nitriles or a-amino phosphonates in high yields (Equation 4.18). This method does not require the use of either an add or base catalyst [40],... 

As the intermediate enamine reacts faster with imines than aldehydes, a one-pot three component coupling of the donor ketone, aldehyde and amine is possible. List and coworkers have achieved high ees in this reaction utilising L-proline (7.66) and some aliphatic aldehydes and aromatic aldehydes such as (7.136) in combination with p-anisidene (7.137). This catalyst system is also effective for the coupling of a-hydroxyketones. Use of the tetrazole-substituted proline (7.80) allows the reaction to be performed in dichloromethane rather than DMSO and high ees in the Mannich reaction between aliphatic ketones and imines derived from ethyl glyoxalate have been obtained imder these reaction conditions. 

Trifluoroethanol (TFE) has been found an efficient and recyclable medium in promoting one-pot, three-component coupling reactions of... 

Both ( )- and (Z)-allyl dithiocarbamates have been stereoselectively prepared in high yields from acetates of MBH adduets in catalyst-free one-pot three-component coupling reactions of carbon disulfide and amine in water under a mild and green procedure (Scheme 3.152). The reaction pathway involves the nucleophilic displacement (-S n2 ) of MBH acetates by dithio-carbamate anions. The utility of these allyl dithiocarbamates has been demonstrated in the synthesis of 3,5-dibenzyl-l,3-thiazines derivatives 344 and 345 (Scheme 3.153). ... 

Srihari, R, Singh, V.K., Bhunia, D.C. andYadav, J.S. 2009. One-pot three-component coupling reaction Solvent-free synthesis of novel 3-substituted indoles catalyzed by PM A-SiOj. Tetrahedron Lett. 50(27) ... 

The reactions initiated by the addition of a carbon-carbon multiple bond to the cation pool bring in unique one-pot transformations otherwise difficult to realize, because the reactive carbocations are existing in the solution in relatively high concentration. For example, a sequential one-pot three-component coupling reactions have been developed (Scheme 5) [9, 10]. [4 -f 2] cyclo addition reactions in which an N-acyliminium ion was used as a hetero diene [11], and cationic carbohydroxylation of alkenes and alkynes using the cation pool method [12] were also accomplished. 

Cation-Pool Method, Scheme 5 One-pot three component coupling... 

The potential of one-pot three-component coupling reaction was further explored by the same group for the synthesis of substituted tetrahydropyranols 207 Ishikawa [96]. As for the two previous examples, the isolation of the Michael products A in suitable yields is only allowed when the addition of the different starting materials proceeds in a well-established order, thus avoiding undesired side reactions. Furthermore, this three-component coupling process could be successfully combined with an additional nucleophilic addition step to allow an asymmetric one-pot four-component coupling reaction to give rise to tetrahy-dropyrans 208 that are present in many natural products (Scheme 2.70). 

N. Sakai, N. Uchida, T. Konakahara, Synlett 2008, 1515-1519. Facile and selective synthesis of propargylic amines and 1,6-diynes one-pot three-component coupling reactions of alkynylsilanes, aldehydes and amines by a cooperative catalytic system comprised of CuCl and Cu(OTf)j. 

The method for the synthesis of a,-aminonitriles through a one-pot three-component coupling of aldehydes, amines, and trimethylsilyl cyanide using a catalytic amount of bismuth(III) chloride was reported. The reaction was successful using both primary and secondary amines with a variety of aldehydes but not ketones. Moreover, acid-sensitive aldehyde such as furfuraldehyde afforded with high yield (Equation 15) [33ej. 

In Chap. 3, the author describes two direct routes to 1,2,3,4-tetrahydro-/ -carboline derivatives by a copper-catalyzed one-pot three-component coupling-indole formation-nucleophilic cyclization at the 3-position of indole. 

In 2005, Xi and coworkers reported that 1,1-cycloaddition of oxalyl chloride with l,4-dilithio-l,3-dienes 379 or zirconcyclopentadienes 397 afford CPDNs 399 in the presence of CuCl (Scheme 6.100a), in which the carbon-carbon bond of the 1,2-dicarbonyl component cleaves during nucleophilic addition [239]. They also found that no reaction is observed when 397 is treated with isocyanates. However, multiply substituted ICPDs 400 are formed from Lewis acid-promoted reactions (BF3-Et20) by a one-pot three-component coupling process (Scheme 6.100b) [240]. 

Naresh G, Kant R, Narender T (2014) Copper(II) catalyzed expeditious synthesis of furoquinox-alines through a one-pot three-component coupling strategy. Oig Lett 16 4528-4531. doi 10. 1021/ol502072k... 

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