Heck-type reactions intramolecular

Dimethyl iodo(4-pentenyl)malonate (926) undergoes a Pd-catalyzed intramolecular radical-type reaction to form the alkyl iodides 927 and 928. rather than a Heck-type reaction product(775]. The same products are also obtained by a radical reaction promoted by tin hydride(776]. Although yield was low, a similar cyclization of the n-chloro ester 929 to form the seven-membered ring 930 was ob,served(777(. 

Another sequence involving an anionic and a Pd-catalyzed step was described by the groups of Rossi and Arcadi [477]. These authors prepared substituted tetrahy-dro-2H-pyrrolo[3,2-c]pyrazolones 2-934 starting from hydrazones 2-932 and aryl-halides or alkenyl triflates 2-933 (Scheme 2.208). The first step is the formation of a pyrazolone. There follows cleavage of the urea moiety with piperidine and an inter-as well as an intramolecular Heck-type reaction with 2-933. 

A similar approach was used by the Alcaide group [183] in the synthesis of tricyclic (3-lactams 6/1-391 from 6/1-390 (Scheme 6/1.99). In this domino process the primarily obtained it-allyl-Pd-complex reacts with the N-nucleophile of the urethane moiety to form a C-N-bond and a vinyl halide. The final step is then an intramolecular Heck-type reaction of the vinyl halide with the alkyne moiety and re-... 

Compounds similar to the above may also be obtained by an intramolecular Heck-type reaction of the bromo compound 103. Treatment of 103 with palladium(ll) acetate gives a mixture of two isomers, of which the major is 104 (with the more extended conjugation) (Equation 20) <1995JOC2312>. 

In the cyclization of the (iodoaryl)diene, N-methyl-N-(l,5-hexadiene-3-yl)-2-iodobenzoic acid amide, the combined yield of the tricyclic products arising from a double intramolecular Heck reaction reached 52 % when the catalyst was prepared from [Pd(OAc)2] and 1,10-phenanthroline and the reaction was run in ethanol/water 1/1 (Scheme 6.4) [18,19]. Interestingly, in CH3CN the reaction did not proceed at all with this catalyst. It is also noteworthy, that Pd-phenanthroHne complexes are rarely used as catalysts in Heck-type reactions. 

This section did not appear in CHEC-I(1984) and CHEC-II(1996) <1984CHEC(2)1, 1996CHEC-II(6)1>. Examples are the intramolecular Heck-type reaction of 2-benzyl-5-(2-bromophenyl)-4-phenylpyridazin-3(2//)-one and 5-(2-bromophenyl)-2-methyl-6-phenylpyridazin-3(2//)-one which yields 2-benzyldibenzo[/, ]phthalazin-l(2//)-one and 2-methyldibenzo[/,. ]cinnolin-3(270-one, respectively <2003T5919>. The same compounds were also obtained from the corresponding 2-aminophenyl (instead of 2-bromophenyl) derivatives via diazotization and subsequent Pschorr reaction. 

Intramolecular Heck-type reaction of 2-bromo-A -(I//-indol-l-yl)-A -methylnicotinamide 241 yielded tetracyclic 6-methylpyrido[3, 2 4,5]-pyridazino[I,6- ]indol-5(6//)-one 242 in 92% yield (Equation 57) <1995TI94I>. 

A single alkyne relay is involved in the cascade oligocyclizations of 2-bromoalka-l,w-diene-//-ynes such as 90, 92, 94 and others. Three new rings are formed in these sequences of two intramolecular Heck-type reactions and a 67r-electrocyclization leading to various oligocyclic systems such as 91, 93, 95 in a rather elegant way (Scheme 25). - ... 

Scheme 25 Formation of three new rings from 2-bromoalka-1, m-dien-n-ynes in a domino sequence of two intramolecular Heck-type reactions and 67r-electrocyclization...

The transformations of 136 proceed cleanly upon treatment with a catalytic amount of Pd(PPh3)4, in the presence of triethylamine and molecular sieve (MS) 4 A it apparently is initiated by oxidative addition of the N(sp )-0 bond of 136 to the Pd(0) complex, and this is succeeded by two or even three intramolecular carbopalladations followed by / -hydride elimination. This Heck-type reaction is not affected by the configuration of the oxime derivatives probably due to a facile enough if/Z-isomerization of the alkylideneaminopalladium intermediate. 

The formation of compound 175 could be rationalized in terms of an unprecedented domino allene amidation/intramolecular Heck-type reaction. Compound 176 must be the nonisolable intermediate. A likely mechanism for 176 should involve a (ji-allyl)palladium intermediate. The allene-palladium complex 177 is formed initially and suffers a nucleophilic attack by the bromide to produce a cr-allylpalladium intermediate, which rapidly equilibrates to the corresponding (ji-allyl)palladium intermediate 178. Then, an intramolecular amidation reaction on the (ji-allyl)palladium complex must account for intermediate 176 formation. Compound 176 evolves to tricycle 175 via a Heck-type-coupling reaction. The alkenylpalladium intermediate 179, generated in the 7-exo-dig cyclization of bro-moenyne 176, was trapped by the bromide anion to yield the fused tricycle 175 (Scheme 62). Thus, the same catalytic system is able to promote two different, but sequential catalytic cycles. 

The replacement of a halogen by a low-valent ferrate catalyst is the key step in an intramolecular Heck-type reaction using both alkyl and aryl halides (Scheme 7.7) [11]. 

A similar palladium-catalyzed process involving an intramolecular Heck-type reaction in the first step was developed by Grigg and co-workers [70], The resulting seven-membered ring vinylpalladium(II) intermediate 54 reacts with the allene to... 

A broad variety of special aldehydes and ketones are easily accessible by Heck-type reactions with allylic alcohols and their homologs [3]. The potential for the synthesis of carbocydic structures is illustrated by the macrocyde 11 [4] which obviously is the product of a fourfold Heck reaction (Scheme 3). A domino process consisting of a double Heck reaction followed by an intramolecular Aldol condensation leads to the annulated ring system 15 [5]. 

For an intramolecular asymmetric Heck-type reaction of alkenyl iodide 73 to form an optically active indolizidine derivative, a palladium catalyst coordinated... 

Whereas inter- and intramolecular Diels-Alder reactions normally require electron-deficient dienophiles, the 67r-electrocyclization proceeds with a large vaiiety of substituents on a hexatriene. In one such approach, the intramolecular Heck-type reaction of a 2-bromo-1 -en-(ft> — l)-yne 66 is used as a trigger to initiate an intermolecular Heck coupling with an alkene to form the conjugated 1,3,5-hexatriene 67 which eventually cyclizes in a 67T-electrocyclic process (Scheme 3-21) [173]. In many cases, aromatization of the cyclohexadiene 68 formed primarily occurs to yield carbo- and heterobicyclic compounds of type 70 [173a,b]. But with alkyl ethenyl ethers the cyclohexadienes 69 can be obtained in moderate yields [173b]. 

For the construction of highly condensed polycyclic skeletons, the cascade consisting of two intramolecular Heck-type reactions and a 67r-electrocyclization as performed with the... 

Although intermolecular Heck-type reactions of carbocyclic arenes are uncommon, related intramolecular reactions are well precedented as illustrated by the following two examples [73, 74]. 

The pioneering studies in this area were reported in 1999 by Narasaka, who demonstrated intramolecular heteroatom Heck-type reactions of 0-pentafluorobenzoyl oximes [97]. As shown below, treatment of unsaturated substrate 97 with a catalytic amount of Pd(PPh,y in the presence of triethyl amine provided pyrrole 98 upon workup with chlorotrimethylsilane. The mechanism of this reaction proceeds via oxidative addition of the N—O bond to afford 99, which undergoes alkene insertion into the Pd—N bond to provide alkyl-palladium complex 100. The exo-methylene product 101 is generated by [i-hydride elimination from 100, and isomerization to the desired pyrrole 98 occurs when chlorotrimethylsilane is added. 

Coordinating the triply sulfonated analog, TPPTS, to palladium has led to improvements in CCBF reactions. For example, Genet previously reported the selective intramolecular Heck-type reaction of various substrates to produce the cyclized product in good yield (Eq. 5) intramolecular Heck coupling [18]. One of the most important features of the Pd(TPPTS)3 catalyst involves the regioselectivity associated with the reaction. For these types of reactions, carried out in organic media, the exo product is usually favored. However, with the use of this catalyst, the endo species was the predominant product. 

Intramolecular Heck-type reaction initiated by palladation of alkenyl Inflates to generate... 

Intramolecular or intermolecular Heck-type reactions were also used in the synthesis of poly-substituted quinoline compounds. Palladium-catalyzed reaction between vinyl or aryl halides and ortAo-allyl-substituted-A -tosyl-anilides produces dihydroquinolines in an intermolecular fashion, where reaction of acrylates intramolecularly affords 4-quinolones. ° ° ... 

Intramolecular oxypalladation of 5,6-dienoic acid 252 is followed by acrolein insertion to generate 254, which undergoes protonolysis to produce the aldehyde 253 without giving elimination product as a Heck-type reaction. The reaction proceeds with a catalytic amount of Pd(OAc>2 in the presence of LiBr, which plays an important role in inhibiting j6-H elimination in 254 [108]. Reaction of 252 in the presence of Pd(OAc>2, Cu(OAc), LiBr and O2 in MeCN provided alkenyl bromide 255 [109]. 

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