Cyclocarbonylations

Unusual cyclocarbonylation of allylic acetates proceeds in the presence of acetic anhydride and an amine to afford acetates of phenol derivatives. The cinnamyl acetate derivative 408 undergoes carbonylation and Friedel-Crafts-type cyclization to form the a-naphthyl acetate 410 under severe condi-tions[263,264]. The reaction proceeds at 140-170 under 50-70 atm of CO in the presence of acetic anhydride and Et N. Addition of acetic anhydride is essential for the cyclization. The key step seems to be the Friedel-Crafts-type cyclization of an acylpalladium complex as shown by 409. When MeOH is added instead of acetic anhydride, /3,7-unsaturated esters such as 388 are... 

In 1991, El-Ali and Alper reported the cyclocarbonylation reaction of terminal propargyl alcohols with formation of 5,5-disubstituted 2(5//)-furanones using Pd(dba)2 and l,4-bis(diphenylphosphino)butane (dppb) (91JOC4099). However, this reaction was not applicable to internal alkynols. 

Chiral lactones were also obtained by cyclocarbonylation of chiral acetylenic alcohols with Pd and thiourea (H2NCSNH2) (Scheme 32). No loss in chirality was observed, but large amounts of Pd and thiourea were used (10 mol %) since the catalyst deactivates by forming metal particles. The catalytic precursor (Pdl2 > PdCl2) and the ratio of thiourea to Pd were very important, thiourea being necessary for this reaction. The active species was supposed to be [Pd(thiourea)3l]I, which forms in situ from [Pd(thiourea)4]l2 and [Pd(thiourea)2]l2. It had to be a partially dissociated species since [Pd(thiourea)4](Bp4)2 was inactive [121]. 

Chiral lactones were also formed by cyclocarbonylation [ 122] with chiral catalysts, such as Pd-poly-L-leucine catalytic system. For example, but-2-en-l-ol led to the corresponding cychc chiral lactone in the presence of Pd catalysts with chiral ligands (Scheme 33). About 10 mol% of Pd(II) chloride... 

Cyclocarbonylation of pyrrole 160 leads in modest yield to 4-acetoxyindole 161 [116]. 

Hidai and co-workers found that 3-vinylindole 326 undergoes cyclocarbonylation to afford 1-acetoxycarbazole 327 [425]. The reaction of indole with allene and CO in the presence of catalytic Pd(0) leads to Af-acylation (328) in good yield [426], An analogous reaction with 5-hydroxyindole affords N- and O-acylation products (47% yield). 

Substituted propargylic alcohols were found to undergo direct carbonylation to the corresponding butenolides in 67-98% yield (Eq. 9.120) [86]. This reaction requires a catalytic amount of Pd2(dba)3-CHC13 (4%) and l,4-bis(diphenylphosphi-no)butane (8%) in CH2C12 under an atmosphere of CO (600 psi) and H2 (200 psi) at 95 °C for 36 h. The cyclocarbonylation reaction is believed to proceed via an allenyl-palladium intermediate, which is formed by initial insertion of Pd(0) into the C-O bond of the alkynol followed by rearrangement (Scheme 9.25). 

Scheme 9.25 Possible mechanism for Pd-catalyzed alkynol cyclocarbonylation.

Scheme 16.31 Formation of a seven-membered lactone via Ru-catalyzed cyclocarbonylation.

The Ru-catalyzed cyclocarbonylation of a-allenic sulfonamides proceeds in the presence of Et3N under a CO atmosphere (20 atm) to yield ,/funsaturated lactams (Scheme 16.32) [36], In order to gain an insight into the reaction mechanism, a deuterium-substituted a-allenic sulfonamide was subjected to the carbonylation. The deuterium was found to be totally transferred to the methyl group. Based on this observation, a mechanism has been proposed which involves a ruthenacycle derived from addition of the Ru-H to the terminal double bond of allene (Scheme 16.33). 

The use of heterogeneous catalysts in this reaction has also been achieved palladium-montmorillonite clays [93] or palladium/activated carbon [94] in the presence of dppb transformed 2-allylphenols into lactones, the regiose-lectivity of the reaction being largely dependant on the nature of the support. Very recently, palladium complexes immobilized onto silica-supported (polyaminoamido)dendrimers were used as catalysts in the presence of dppb for the cyclocarbonylation of 2-allylphenols, 2-allylanilines, 2-vinylphenols, and 2-vinylanilines affording five-, six-, or seven-membered lactones and lactams. Good conversions are realized and the catalyst can be recycled 3-5 times [95]. 

In order to obtain lactones from natural alkenols, we investigated the cyclocarbonylation of monoterpenic alcohols. The catalytic precursor is [PdCl2L2] in the presence of a slight excess of tin chloride and phosphine ligands. Dihydromyrcenol, a representative acyclic terpene containing a termi-... 

Scheme 13 Formation of a six-membered lactone in the cyclocarbonylation of geraniol...

Scheme 15 Asymmetric cyclocarbonylation of an alkenol in the presence of the BICP chiral ligand...

Applying more drastic conditions (100 bar of CO 175 °C), [Rh6(CO)i6] also catalyzes cyclocarbonylation of 2-alkynylphenols. The mechanism involves here also an 0 - H oxidative addition initial step. The a-methylene lactone is further reduced since rhodium catalyzes the water-gas-shift reaction and water is present in the medium [145]. 

Additionally, when Pd-catalyzed cyclocarbonylation of alkynols is carried out in the presence of a large excess of CuCl2 (5 equivalents), (Z)-a-chloroalkylidene-/Mactones are obtained as depicted in Scheme 26 [146,147]. As previously mentioned concerning the intermolecular alkoxycarbonyla-... 

For unsaturated lactones containing an endocyclic double bond also the two previously described mechanisms are presumably involved and the regio-selectivity of the cyclocarbonylation is governed by the presence of bulky substituents on the substrate. Inoue and his group have observed that the catalyst precursor needs to be the cationic complex [Pd(PhCN)2(dppb)]+ and not a neutral Pd(0) or Pd(II) complex [ 148,149]. It is suggested that the mechanism involves a cationic palladium-hydride that coordinates to the triple bond then a hydride transfer occurs through a czs-addition. Alper et al. have shown that addition of dihydrogen to the palladium(O) precursor Pd2(dba)3/dppb affords an active system, in our opinion a palladium-hydride species, that coordinates the alkyne [150]. 

Ring closure with formation of heterocyclic derivatives may occur when a nucleophilic function is present in the starting alkene and it is suitably placed for cyclization [30-43]. Both kind of the mechanistic pathways shown in path a of Scheme 3 and in Scheme 4 may operate, as exemplified by Schemes 5-6 (Y = O, NR). Clearly, only in the first case carbon monoxide is incorporated into the heterocyclic ring (cyclocarbonylation). 

All these reactions are examples of oxidative cyclocarbonylation-alkoxy-carbonylation. However, the Pdh/KI catalytic system turned out to be a very efficient catalyst also for promoting cyclization-alkoxycarbonylation processes. In fact, optimal conditions were found for selectively converting 4-yn-l-ols into tetrahydrofuran derivatives (Eq. 41) [107] through 5-exo-dig cyclization followed by alkoxycarbonylation (Scheme 19, path a). This kind of process was not possible for the propynyl, 3-yn-l-ol, and 2-ethynylaniline substrates, seen before, for stereoelectronic reasons [302], With the latter substrates, the endo cyclization mode (Scheme 19, path b), although in principle stereo electronically allowed, was not observed. 

Carbonylation of (diene)ZrCp2 complexes gives cyclopentenones (Scheme 36)51. Since the relative rates of this carbonylation parallel the relative rates for envelope flip of these cr2, n complexes, it might be speculated that initial coordination of CO to the diene complexes (Scheme 36)157. 

Design of Reactions Starting from Insertion into a Rh-Si Bond 125 Tab. 6.7 Silylative cyclocarbonylation of 63 catalyzed by Rh4(CO)i2-... 

Benzodiazocines 182 and 183 were obtained through a sequence of Ugi-depro-tection-carbonylation/intramolecular amidation using ort/io-iodobenzaldehyde and a bifunctional acid or amine [146] (Fig. 36). This cyclocarbonylation was carefully optimized and succeeded in affording 8-membered lactams, which are typically difficult to obtain, in good yields. 

Onitsuka et al. [27] have developed a novel qfclocarbonylation of l,l -bis[(trimethyl-silyl)ethynyl]ferrocene catalyzed by [Ru3(CO)i2] under CO. Treatment of l,l -bis ((trimethylsilyl)-ethynyl)ferrocene 81 with Ru3(CO)i2 (5 mol%) under CO pressure (lOkgcm ) in toluene at 150 °C for 24h gave the cyclocarbonylation product 82 in... 

Cyclocarbonylation of o-iodophenols 503 with isocyanates or carbodiimides and carbon monoxide in the presence of a catalytic amount of a palladium catalyst (tris(dibenzylideneacetone)dipalladium(O) Pd2(DBA)3) and l,4-bis(di-phenylphosphino)butane (dppb) resulted in formation of l,3-benzoxazine-2,4-diones 504 or 2-imino-l,3-benzoxazin-4-ones 505 (Scheme 94). The product yields were dependent on the nature of the substrate, the catalyst, the solvent, the base, and the phosphine ligand. The reactions of o-iodophenols with unsymmetrical carbodiimides bearing an alkyl and an aryl substituent afforded 2-alkylimino-3-aryl-l,3-benzoxazin-4-ones 505 in a completely regioselective manner <1999JOC9194>. On the palladium-catalyzed cyclocarbonylation of o-iodoanilines with acyl chlorides and carbon monoxide, 2-substituted-4f/-3,l-benzoxazin-4-ones were obtained <19990L1619>. 

The catalytic cyclocarbonylations of diynes proceed efficiently to afford fused cyclohexadienes via trapping of the ruthenacyclopentadiene intermediate by an alkene component <2000JA4310>. Thus, the ruthenium-catalyzed cyclo-co-trimerization of 1,6-heptadiyne derivatives possessing a heteroatom at the 4-position affords heterotricycles in good yields (Equation 110). 

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