Allenes domino reaction

One productive facet of Pd-catalyzed domino reactions is the cycloisomerization of enynes and allenes, as shown by Trost and coworkers [19]. Thus, transformation of the dienyne 6/1-10 using Pd(OAc)2 led to 6/1-13 in 72% yield, in which the last step is a Diels-Alder reaction of the intermediate 6/1-12 (Scheme 6/1.2). 

As shown in the preceding examples, although intramolecular Pd-catalyzed poly-cyclization is a well-established procedure, some few examples exist of polycycliza-tions where the first step is an intermolecular process. In this respect, the Pd°-cata-lyzed domino reaction of allenes in the presences of iodobenzene reported by Tanaka and coworkers [40] is an intriguing transformation. As an example the Pd-catalyzed reaction of 6/1-60 in the presence of iodobenzene led to 6/1-61 in 49% yield, allowing the formation of three rings in one sequence (Scheme 6/1.14). 

As described in the preceding sections, many domino reactions start with the formation of vinyl palladium species, these being formed by an oxidative addition of vinylic halides or triflates to Pd°. On the other hand, such an intermediate can also be obtained from the addition of a nucleophile to a divalent palladium-coordinated allene. Usually, some oxidant must be added to regenerate Pd11 from Pd° in order to achieve a catalytic cycle. Lu and coworkers [182] have used a protonolysis reaction of the formed carbon-palladium bond in the presence of excess halide ions to regenerate Pd2+ species. Thus, reaction of 6/1-386 and acrolein in the presence of Pd2+ and LiBr gave mainly 6/1-388. In some reactions 6/1-389 was formed as a side product (Scheme 6/1.98). 

A domino reaction, whereby up to four equivalents of a nitrile can be added to dilithiated allenes, is believed to proceed via a novel rearrangement. ... 

A different domino reaction yet involving rather similar steps, i.e. car-bopalladation of an allene and nucleophilic attack of a phenol, was elaborated by the same group and leads to isoxazolidines 138 after intramolecular cycloaddition in the intermediates 137 [81] (Scheme 21). This transformation was performed with several aryl and hetaryl iodides 48 and gave the highest yields with electron-rich aryl iodides while only traces of products were obtained starting from electron-deficient aryl iodides. 

Efficient domino reactions of the alkenyl iodide 453 with CO, aUene, and piperidine proceeded to give 456 in very high yield (80 %) after six-step reactions [172], CO is the most reactive, and CO insertion is followed by olefin insertion to generate 454. Then allene insertion occurs after the second CO insertion. Finally, the TT-allylpalladium intermediate 455 is trapped by the amine to yield 456. 

Since the insertion of CO in palladium-catalysed domino reactions can also be part of the first step after an oxidative addition, the combination with a Mizoroki-Heck reaction as the second step has been also investigated. In this context, Okuro and Alper [133] and Grigg et al. [134] described a palladium-catalysed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO (Scheme 8.66). Reaction of 258 or 259 with 260 in the presence of palladium(O) under a CO atmosphere (1 atm) led to the... 

A reductive homocondensation of ( )-benzylidenepyruvate esters promoted by P(NMe2)3 affords polyfunctionalized 3,4-dihydro-2f/-pyrans (130L1926). Enantiopure 5,6-dihydro-2f/-pyrans are accessible from a chemo- and regio-controlled palladium(II)-catalyzed domino reaction of P,Y-allenediols with a-allenic acetates (Scheme 3) (13CEJ14233). 

In 2007, Shibasaki et al. reported a three-component domino reaction induced by cooperative catalysis between copper and zinc. This novel domino reaction occurred between acetophenone, diethylzinc and an allenic ester, providing the corresponding chiral lactone in high yield and excellent enantioselectivity of 96% ee, as shown in Scheme 3.1. The process began with the addition of diethylzinc to the allenic ester, which was followed by an aldolisation with acetophenone, and a lactonisation reaction gave the final product. Initially, the Cu(ii) was reduced to Cu(i) in the presence of... 

Grigg et al. reported a successful four-component domino reaction for the synthesis of functionalized dienes 316 from aryl iodides, allyl amine derivative, allene, and carbon monoxide [110] (Scheme 6.83). Carbon monoxide could insert into the C—Pd bond of arylpalladium(II) iodides to generate a carbonylpalladium species, which is followed by allenylation to form n-allylpalladium species. Finally, the attack of the nitrogen nucleophile produces the product observed. The products of this domino multicomponent reaction could be subjected efficiently to ring-closing metathesis in the presence of Grubbs second-generation catalyst. 

Recently, a further unique domino methodology has been reported by Lu and coworkers (Scheme 2.74) [173]. Herein, a triphenyl phosphine-catalyzed umpolung addition/cyclization of allenes and alkynes containing an electron-withdrawing group 2-316-2-318 followed by reaction with a double nucleophile 2-319 is assumed to account for the production of a broad palette of various heterocycles 2-321 and 2-323 via 2-320 and 2-322, respectively. Dihydrofurans, piperazines, morpholines and diazepanes were obtained during the process. 

Several Pd-catalyzed domino processes start with a Tsuji-Trost reaction, a pal-ladation of alkynes or allenes [5], a carbonylation [6], an amination [7] or a Pd(II)-cat-alyzed Wacker-type reaction [8]. A novel illustrious example of this procedure is the efficient enantioselective synthesis of vitamin E [9]. 

A regio- and diastereoselective Pd-catalyzed domino silastannylation/allyl addition of allenes 6/1-236 containing a carbonyl moiety with Bu3Sn-SiMe3 6/1-237 is described by Kang and coworkers [117]. The reaction allows the synthesis of hetero-and carbocyclic compounds with a ring size of five and six. It can be assumed that... 

Another versatile domino process for the synthesis of carbocycles as well as heterocycles is the Pd-catalyzed reaction of organic halides or triflates with alkynes or allenes, which contain a carbo- or heteronucleophile in close vicinity to these functionalities (see Scheme 6/1.75) [133]. 

Knoke and de Meijere [60] recently developed a highly flexible domino Heck-Diels-Alder reaction of a symmetrically substituted cumulene 125, which also involves cross-couplings of an allene at the central position. Both aryl and hetaryl halides react efficiently with l,3-dicyclopropyl-l,2-propadiene (125) and furnish 1,3,5-hexatriene derivatives 126 as intermediates, which are usually trapped by acceptor-substituted olefins in a subsequent cycloaddition, providing adducts 127a/b in moderate to good overall yields (Scheme 14.30). 

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