Three-component tandem coupling reaction

Overman and co-workers [75] prepared alkenyltins via a vinyl triflate/ditin coupling. Mitchell and Kwetkat developed a simple route to acyltrimethylstannanes [187], whereas Hitchcock et al. [ 188] carried out a three-component tandem coupling reaction by reacting a 2-pyridyl triflate, aryl or heteroaryl bromides, and hexamethylditin with Pd(PPh3)4 the presence of LiCl to give azabiai yls (Scheme 4-48). 

The synthesis of the promazine 444 class of antipsychotics was pursued by medicinal chemists firom Lundbeck Pharmaceuticals (Deerfield, EL). Although the C—N and C S bond formations have been separately developed and optimized to practical use, the formation of multiple carbon-heteroatom bonds has been challenging. To this end, the researchers developed a palladium-catalyzed, three-component cross-coupling reaction in which the formation of one C—S bond from thiophenol 441 and aromatic halogenide 443 and two C—N bonds from amines 442 were accomplished in a one-pot tandem reaction fashion (Scheme 46.50). 

Cycloisomerization represents another approach for the construction of cyclic compounds from acyclic substrates, with iridium complexes functioning as efficient catalysts. The reaction of enynes has been widely studied for example, Chatani et al. reported the transformation of 1,6-enynes into 1-vinylcyclopentenes using [lrCl(CO)3]n (Scheme 11.26) [39]. In contrast, when 1,6-enynes were submitted in the presence of [lrCl(cod)]2 and AcOH, cyclopentanes with two exo-olefin moieties were obtained (Scheme 11.27) [39]. Interestingly, however, when the Ir-DPPF complex was used, the geometry of olefinic moiety in the product was opposite (Scheme 11.28) [17]. The Ir-catalyzed cycloisomerization was efficiently utilized in a tandem reaction along with a Cu(l)-catalyzed three-component coupling, Diels-Alder reaction, and dehydrogenation for the synthesis of polycyclic pyrroles [40]. 

The Lee group originated rhodium alkenylidene-mediated catalysis by combining acetylide/alkenylidene interconversion with known metal vinylidene functionalization reactions [31], Thus, the first all-intramolecular three-component coupling between alkyl iodides, alkynes, and olefins was realized (Scheme 9.17). Prior to their work, such tandem reaction sequences required several distinct chemical operations. The optimized reaction conditions are identical to those of their original two-component cycloisomerization of enynes (see Section 9.2.2, Equation 9.1) except for the addition of an external base (Et3N). Various substituted [4.3.0]-bicyclononene derivatives were synthesized under mild conditions. Oxacycles and azacycles were also formed. The use of DMF as a solvent proved essential reactions in THF afforded only enyne cycloisomerization products, leaving the alkyl iodide moiety intact. 

Kobayashi S, Akiyama R, Moriwaki M, Three-component or four-component coupling reactions leading to 6-lactams, Facile synthesis of y-acyl-6-lactams from silyl enolates, a, /l-unsaturated thioesters, and imines or amines and aldehydes via tandem Michael-imino aldol reactions, Tetrahedron Lett., 38 4819—4822, 1997. 

Hi. Carbon-silicon bonds. Following the earlier reports mentioning the palladium-catalysed addition of organosilylstannanes to alkynes or isonitriles , Mori and coworkers realized tandem transmetallation-cyclization reactions with bifunctional halogeno triflates and Bu3SnSiMe3 18. The reactivity of 18 under palladium catalysis was used for the silylstannylation of alkenes or the synthesis of allylic silanes via a three-component (aryl iodide - - diene - - 18) coupling reaction. Recently, a similar... 

Tandem insertion of aUyl carbenoids and aldehydes affords some organic compounds resnlting from a three-component coupling reaction. The most extensively studied application of this methodology is the insertion of allyl carbenoids into zirconacycles and subsequent elaboration of the formed allylzirconocenes with electrophiles (Scheme 39). ... 

Intermolecular additions of alcohols to alkynes can be coupled with other tandem reactions of the alkenyl-gold intermediate. Thus, reaction between salicylaldehyde and phenylacetylenes can give access to the isoflavanone skeleton (equation 7), whereas a three-component addition of methylenecylopropylcarbinols, arylalkynes, and alcohols leads to bicyclic compounds (equation 8). ... 

A three-component coupling that can be considered as tandem Heck and Stille reactions gives rise to cis-4,5-diaryl-1,3-dioxolane. The reactants are aryl bromides, 1,3-dioxole. and phenyltributylstannane. (Other aryltributylstannanes should also be applicable.)... 

Recent approaches to the copper-catalyzed three-component coupling of organometaUic reagents with imines and acid chlorides employ organoindium compounds [147] or orga-nostannanes [148]. In the first case, a-substimted amides or A -protected amines are obtained, whereas the second process provides hexahydro-l/f-isoindolones via a tandem Cn-cata-lyzed three-component coupling/intramolecular Diels-Alder reaction. 

Furthermore, three-component coupling tandem Michael-aldol reactions were achieved by trapping the aluminium enolate intermediate with an aldehyde (Scheme 19.16a). Initiated by the asymmetric Michael addition of malonic esters to cyclic enones, several natural products were synthesised... 

Kaspar and Ackermann also reported that the process could be performed as a three-component system, featuring in situ generation of the key o-alkynylhaloarenes via the incorporation of a tandem Sonogashira reaction [35]. Related chemistries have been reported for the synthesis of 2-aminoindoles from ynamide-based substrates [36], A-aminoindoles from hydrazine-based nucleophiles [37], and N-unsubstituted indoles via the use of ammonia as the coupling partner [38,39],... 

The tandem reaction of allyl electrophiles with alkynes and MejAl or Mc2Zn occurs in the presence of Ni(acac)2 to give a regioisomeric mixture of the three-component coupling products [234]. The reaction can also proceed intramolecu-larly to give cyclic nonconjugated dienes. 

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