Palladium sequential reactions

Kuroda and Suzuki used reaction of 267a with 2-bromoaniline leading to anilide 312 as the first step of their sequence in the preparation of 1H-imidazo[4,5-c]quinolin-4(5//)-ones (Scheme 77) (91TL6915). Reaction of 267a with amines usually does not require any catalyst and/or base, but in this case use of sodium hydride was reported. The anilide 312 was sequentially alkylated, first with methyl iodide in ethanol with potassium hydroxide at room temperature and then with different alkyl iodides in acetone at reflux to provide intermediate 313. This compound was then cyclized via palladium catalyzed reaction leading to product 314. This reaction provides a new entry to l//-imidazo[4,5-c]quinolin-4(5//)-ones that are of current interest as antiasthmatic agents. 

A closely related variant of this novel strategy has also been applied to the efficacious total syntheses of ( )-haemanthidine (382) and ( )-pretazettine (395) (209). In the event (Scheme 47), sequential reaction of the zinc derivative of the metalloenamine 509 with the protected amino acetaldehyde 516, pivaloyl chloride, and then 3 N HC1 provided an intermediate 8-keto aldehyde, which underwent cycloaldolization and dehydration on treatment with pyrrolidine in 33% aqueous AcOH-MeOH to furnish 517 as a mixture (1.5 1) of diastereo-mers. The a -bromination of 517 with PhNMe3Br3 in EtOAc followed by dehydrobromination with DBU in refluxing benzene then provided the racemic cyclohexadienone 518. Palladium(0)-catalyzed removal of the A-allyloxycar-... 

A domino total synthesis of spirotryprostatin B (2) and three of its isomers has been published by Overman and Rosen, who apply two sequential palladium-catalyzed reactions (one-pot) to assemble the two spiro-fused rings [10] (Scheme 3). This work again makes it clear that complex heterocyclic systems may represent a harder challenge to synthetic... 

If the palladium-catalyzed reaction is performed with a chloroiodoarene as substrate, the stannane reacts faster by the C—I bond via a chemoselective crosscoupling reaction to give an ArCl as product this can be further arylated by a consecutive SRN1—Stille reaction. These sequential reactions can also be carried out with substrates with two leavings groups to afford products in high yields (Scheme 10.31) [41]. 

Abstract Sequentially palladium-catalyzed reactions consist of combinations of identical, related, or significantly different palladium-catalyzed processes that occur in a sequential or consecutive fashion in the same reaction vessel without addition of further amounts of catalyst to the reaction media. This novel type of cascade reaction can be elaborated into both domino and multicomponent processes and represents a significant contribution to the highly topical field of diversity-oriented synthesis. 

Alkynyl(trimethyl)silanes smoothly couple with alkenyl halides at room temperature in the presence of a palladium catalyst and TASF (Eq. 5) [4]. The difference in reactivity between alkynylstannanes and -silanes were utilized in a palladium-catalyzed three component cross-coupling reaction. Thus, the palladium-catalyzed sequential reaction of tributylstannyl(trimethylsilyl)ethyne... 

A catalytic amount of CuCl was found to activate alkynyl(trimethyl)silanes in the palladium-catalyzed coupling reaction with aryl triflates (Eq. 7) [12]. The catalytic cycle is considered to involve the transfer of an alkynyl group from an alkynylsilane to Cu(I) and then to palladium(II). A sequential palladium-catalyzed reaction of trimethylsilylacetylene gives unsymmetrical diarylacet-ylenes (Eq. 8). 

The catalytic generation of alkynones and chalcones by palladium catalyzed reactions is an entry to sequential, consecutive, and domino transformations and opens new routes to heterocycles by consecutive coupling-cyclocondensation or Cl-cyclocon-densation sequences. The advantages are not only the compatibility of similar reaction conditions but also the tunable reaction design that allows the combination of several organic and organometallic elementary reactions to new diversity oriented syntheses. Future developments will address also sequentially catalyzed processes... 

Olefin isomerization catalyzed by ruthenium alkylidene complexes can be applied to the deprotection of allyl ethers, allyl amines, and synthesis of cyclic enol ethers by the sequential reaction of RCM and olefin isomerization. Treatment of 70 with allyl ether affords corresponding vinyl ether, which is subsequently converted into alcohol with an aqueous HCl solution (Eq. 12.37) [44]. In contrast, the allylic chain was substituted at the Cl position, and allyl ether 94 was converted to the corresponding homoallylic 95 (Eq. 12.38). The corresponding enamines were formed by the reaction of 70 with allylamines [44, 45]. Selective deprotection of the allylamines in the presence of allyl ethers by 69 has been observed (Eq. 12.39), which is comparable with the Jt-allyl palladium deallylation methodology. This selectivity was attributed to the ability of the lone pair of the nitrogen atom to conjugate with a new double bond of the enamine intermediate. 

In contrast to palladium and other Group VUI metals. Koto et al. have reported an active carbon-catalyzed hydrogenolysis of CFC-114a (43). The process generally operates at a higher temperature, over 400 C, and appears to produce HCFC-124 and HFC-134a as products of sequential reactions, because the former product is produced in higher proportion. 

In connection with a total synthesis of frondosin B, the key intermediate shown below was synthesized by a sequential reaction of the phenol, the enyne and the bromide in a one-pot operation as shown <04OL457>. The palladium-catalyzed intramolecular C-0 bond formation between aryl halides and enolates was employed to make 2,3-disubstituted benzo[i> furans <04OL4755>. 

Another potentially powerfnl sequence arises by combining one or two intramolecular Heck-type couplings with an intra- or intermolecular Diels-Alder addition (for early examples of inter-intermolecular one-pot domino Heck-Diels-Alder reactions see Refs. [49] and [50]). An all-intramolecular version of such a sequence has been shown to proceed reasonably smoothly for terminally alkoxycarbonyl-substituted 2-bromotrideca-l,ll-dien-6-ynes under palladium catalysis at 130 °C. At 80 °C, the sequential reaction stops after the two consecutive Heck-type cyclizations and subsequent /3-hydride elimination to give a 1,3,6-triene apparently only the ( )-isomer undergoes the intramolecular Diels-Alder reaction, as the (Z)-l,3,6-triene is observed accompanying the tetracyclic system obtained at 130 °C (Scheme 36). 

Scheme 8.69 A palladium-driven zipper-type sequential reaction [404].

Meanwhile, Catellani, Derat and their co-workers developed the synthesis of dihydrodibenzoazepine and dibenzoazepine derivatives from 2-bromoanilines and aryl iodides. The process was based on the sequential reaction of three components, an aryl iodide, a bromoaniline, and either norbornene or norbornadiene in the presence of palladium as the catalyst (Scheme 4.13c). Whereas the use of norbornene leads to dihydrodibenzoazepine derivatives, norbornadiene allows an additional step consisting of a retro-Diels-Alder reaction, thus leading to the parent dibenzoazepines. 

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