Pd-catalyzed 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(. 

The linear dimerization of substituted conjugated dienes is difficult, but the Pd-catalyzed intramolecular dimerization reaction of the 1,3,9,11-tetraene 13 gives the 3-propenylidene-4-allylpiperidine derivative 14, which has the 1,3,7-octatriene system. The corresponding 1,3,8,10-tetraene also affords the 3-pro-penylindene-4-allylcyclopentane derivative[18]. 

Buchwald has developed a route to indolines by the Pd-catalyzed intramolecular amination of aryl halides <96T7525> and applied this method to the synthesis of natural products. Thus, cyclization of tetrahydroquinoline 70 provided 71 which was elaborated to a key intermediate in syntheses of damirones A and B and makuluvamine <96JA1028>. 

Interestingly, treatment of diene 215a with methanesulfonic acid afforded 216 as a single diastereomer in 88% yield, the structure of which was confirmed by X-ray analysis (Scheme 60). The transformation of 216 into 217 started with an alkylation, followed by reductive desulfurization and triazene formation to afford compound 217 in 92% yield. Upon treatment with diiodomethane, triazene 217 was smoothly converted to aryl iodide 218 in 75% yield. Pd-catalyzed intramolecular Heck coupling of 218 led to the desired product 219b in 62% yield. 

A few intriguing developments in the area of tetrahydro-P-carboline synthetic methodology include the report of a catalytic asymmetric Pictet-Spengler reaction <06JACS1086> and an enantioselective Pd-catalyzed intramolecular allylic alkylation of indoles <06JACS1424>. A one-step synthesis of 1-substituted-P-carbolines from L-tryptophan has appeared that bypassed the tetrahydro intermediate <06T10900>. 

Table 2 Heterocyclic compounds from Pd-catalyzed intramolecular reactions...

Pd-catalyzed intramolecular etherification reactions of aliphatic alcohols have also been practiced in tandem with other bond-forming processes, such as a Pd-catalyzed allyltin addition to an aldehyde (Equation (32)).160 Similarly, a tandem C-N and G-O bond formation sequence occurs (Equation (33)) during the reactions of /3-amino alcohols with biscarbonates in the presence of the N,O-acetal-derived ligand 43.161-163... 

In rare cases, the Pd-catalyzed intramolecular allylic etherification has been extended to the construction of medium-sized rings. Both an 11-membered bis-ether ring (Equation (34))164 and an eight-membered ether ring (Equations (35) and (36))155 have been prepared in this fashion. In the latter case, the choice of ligand dictated the regiochemical outcome. 

Among early reported Pd-catalyzed reactions, the Mori-Ban indole synthesis has proven to be very useful for pyrrole annulation. In 1977, based on their success of nickel-catalyzed indole synthesis from 2-chloro-fV-allylaniline, the group led by Mori and Ban disclosed Pd-catalyzed intramolecular reactions of aryl halides with pendant olefins [122]. Compound 102, easily prepared from 2-bromo-lV-acetylaniline and methyl bromocrotonate, was adopted as the cyclization precursor. Treatment of 102 with Pd(OAc)2 (2 mol%), Ph3P (4 mol%) and NaHCQ3... 

Substituting the benzene ring with a double bond, Pd-catalyzed intramolecular alkoxylation of alkyne 122 also proceeded via an alkenyl palladium complex to form furan 123 instead of a benzofurans [99, 100]. In addition, 3-hydroxyalkylbenzo[fc]furans was prepared by Bishop et al via a Pd-catalyzed heteroannulation of silyl-protected alkynols with 2-iodophenol in a fashion akin to the Larock indole synthesis, [101]. 

The synthesis of lycorane (13) by Mori and Shiba-saki121 is breathtaking for its use of three consecutive Pd catalyzed C-C bond forming reactions. Thus, Pd-catalyzed asymmetric allylic substitution of a benzoate in meso 7 in the presence of the chiral bisphos-phine 8 leads to the regioselective formation of 10 in 40 % ee It is easy to overlook this low level of enantioselectivity when we are faced with the subsequent elegant Pd-catalyzed reactions Pd-catalyzed intramolecular animation is followed by a Pd-catalyzed Heck coupling to afford 12, which is then readily converted to the target molecule... 

Scheme 2. Pd-catalyzed asymmetric allylic alkylation of 7 is followed by a Pd-catalyzed intramolecular C-N bond formation and a Pd-catalyzed intramolecular Heck-type alkylation in Mori and Shibasaki s total synthesis of lycorane (1995).

Scheme 3. Pd-catalyzed intramolecular asymmetric allylic alkylation in Genet s synthesis of chanoclavine I (1994).

Using terminal propargylic formates, allenes were prepared much more cleanly by Pd-catalyzed intramolecular reduction [46, 47]. The reduction process can be seen as a kind of decomposition reaction and therefore no additional reductant (ammonium formate) is required. In the Pd-catalyzed self-reduction of 28, the terminal allene 29 was formed in 86% yield with 99% selectivity and only a trace amount of alkyne 30 was detected (Scheme 3.15). 

That the second option can also be successfully used has recently been revealed by our synthesis of 2-methoxyphenazine (117) [90]. The reduction of o-bromo-o -nitrodiphenylamine 132 accessible via intermolecular Pd-catalyzed JV-arylation provides the o-amino-o -bromodiphenylamine 133, which can then be cyclized to give 117 in a Pd-catalyzed intramolecular AT-arylation by employing Pd2(dba)3 as the Pd complex and 134 as the phosphine ligand. It should be noted that the outcome of both the intermolecular and the intramolecular AT-arylations heavily depends on the appropriate choice of the Pd complex as well as the phosphine. Ether cleavage leads to 2-hydroxyphenazine (9). 

The Pd-catalyzed intramolecular aminocarbonylation of trihydroxy-6-amino-l-hexene derivative 212 under ambient pressure of CO gave key precursors to 1-deoxynojirimycin and l-deoxy-/-idonojirimycin, 213 and 214, in moderate to fairly good yields (Equation (15)). The diastereoselectivity of this reaction depends on the reaction conditions and the use of THE as solvent and running the reaction at room temperature favors the formation of 213, which is the key precursor to 1-deoxynojirimycin, while the reaction in acetic acid at 50 °C affords 214, the key precursor to l-deoxy-/-idonojirimycin. 

The Pd-catalyzed intramolecular aminocarbonyiation has also been applied to the formal total synthesis of Anatoxin-A 219, an acetylcholine mimic (Equation (16)). Thus, the reaction of 5-(methoxycarbonylamino)-cyclooctene 216a in the presence of a catalytic amount of PdCl2 and cupric chloride (CUCI2) (3 equiv.) in methanol under ambient pressure of CO gave the desired azabicyclo[4.2.1]nonane 217 as the predominant product. The regioselectivity of this reaction is highly dependent on the nature of the A -substituent. Thus, the... 

Pd-catalyzed Intramolecular Alder-ene Reaction of 1,6- and 1,7-Diynes and Enynes... 

Hennings, D. D. Iwasa, S. Rawal, V. H. Anion-accelerated Pd-catalyzed intramolecular coupling of phenols with aryl halides./. Org. Chem. 1997, 62, 2-3. 

Pd-catalyzed intramolecular ene reactions.s Both this complex and bis(dibenzylideneacetone)palladium, Pd(dba)2, have been used to effect this intramolecular cyclization of dienes capable of forming allylpalladium complexes. 

Formation of O- and N-heterocycles by Pd-catalyzed intramolecular 1,4-addition reactions of conjugated dienes 92PAC429. 

Pd-Catalyzed intramolecular amination of olefins leading to N-heterocycles 91MI40. 

After James and Stille had shown the general possibility to link (intermolecular) alkoxypalladation and carbonylation processes 4], Semmelhack et al. were the first to achieve Pd-catalyzed intramolecular alkoxycarbonylation reactions and to apply them in the synthesis of specific target molecules [5]. In a typical reaction, the substrate is stirred at room temperature in methanol under an atmosphere of CO (I. I atm) in the presence of 5-10 mol% of PdCl2 and an excess (3 eq.) of CuClj. As the conversion of the simple model compound 4 to the products 5 and 6 implies, such reactions often proceed in good yields but not necessariliy with high diastereoselectivies (5 6 = 3 I). 

The Pd-catalyzed intramolecular arylation involving C (sp2)-H activation gave a library of fused pyridoimidazoquinolinones (iii). The green synthesis afforded the polycyclic derivatives in good yields [8]. 

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