Tandem reactions alkoxycarbonylation

For that reason an intramolecular benzannulation was developed, which incorporates all components for the intramolecular alkoxycarbonylation into the naphthoquinone 105 [65]. Based on that strategy a short and convergent pathway for the synthesis of racemic deoxyfrenolicin 108 was accomplished. Xu et al. replaced the allylacetylene 100 in the reaction sequence for nanaomycin A by alkynoate 106. The benzannulation product 107 was an appropriate precursor for a subsequent tandem oxa-Pictet-Spengler cyclisation/DDQ-induced coupling reaction [66]. Following this strategy the total synthesis of enan-tiomerically pure deoxyfrenolicin could be accomplished (Scheme 48). 

Two other Ni(CO)4 substitutes, Ni(CO)3PPh3 and Ni(COD)2/dppe, prove to be appropriate for the catalysis of tandem metallo-ene/carbonylation reactions of allylic iodides (Scheme 7)399. This process features initial oxidative addition to the alkyl iodide, followed by a metallo-ene reaction with an appropriately substituted double or triple bond, affording an alkyl or vinyl nickel species. This organonickel species may then either alkoxycar-bonylate or carbonylate and undergo a second cyclization on the pendant alkene to give 51, which then alkoxycarbonylates. The choice of nickel catalyst and use of diene versus enyne influences whether mono- or biscyclization predominates (equations 200 and 201). 

We have reported on a tandem procedure for the synthesis of 3-allyl-N-(alkoxycarbonyl)indoles 115 via the reaction of 2-(alkynyl)phenylisocyanates 114 and allyl carbonates 5 in the presence of Pd(PPh3)4 (lmol%) and CuCl (4 mol%) bimetallic catalyst [80]. A proposed mechanism is shown in Scheme 35. Initially, the insertion of the isocyanates 114 into the complex 7, formed by the reaction of 5 with Pd(0), would form the 7r-allylpalladium intermediates 117. This intermediate, with Pd - N bonding, could be in equilibrium with the Pd - O bonded intermediates 118, which should more probably be represented as the bis-7r-allylpalladium analogue 119. Insertion of the alkyne then occurs to form the indoles 115 and the Pd(0) species is regenerated. It should be emphasized that no carboamination takes place at all in the absence of CuCl the product 116 was obtained. 

Miyabe et al. developed a tandem addition/cycUzation reaction featuring an unprecedented addition of alkoxycarbonyl-stabihzed radicals on oxime ethers [117], and leading to the diastereoselective formation of /1-amino-y-lactone derivatives [118,119]. The reaction proceeds smoothly in the absence of toxic tin hydride and heavy metals via a route involving a triethylborane-mediated iodine atom-transfer process (Scheme 37). Decisive points for the success of this reaction are (1) the differentiation of the two electrophilic radical acceptors (the acrylate and the aldoxime ether moieties) towards the nucleophilic alkyl radical and (2) the high reactivity of triethylborane as a trapping reagent toward a key intermediate aminyl radical 125. The presence of the bulky substituent R proved to be important not only for the... 

This radical can be quenched by tin hydride, but still is able to undergo tandem C-C bond-forming reactions if a rationally designed system follows. However, as summarized in Scheme 6, tandem sequences have to overcome the problem of isomerization to the thermodynamically more stable six-membered radical [26], Table 2 lists several examples of cyclopentanone synthesis based on a 4+1 radical annu-lation process. The first example shown in Table 2 demonstrates that the 4-hexenyl radical/CO system faces this isomerization problem, which is difficult to suppress [27, 26a]. Of course, some substituents, such as phenyl and alkoxycarbonyl groups, are effective in hindering such an isomerization process from 5 to 6 (runs 2, 3, 4) [27]. 

Leighton et al. described an effective and nuld palladium-catalyzed tandem alkene addition/carbonylation procedure in the synthesis of leucascandrolide A [50]. Intramolecular alkoxycarbonylation of diol 65 under Semmelhack conditions proceeded efficiently to provide the desired 2,6-cis-tetrahydropyran 66 in 75 % yield with a dr of >10 1 (Scheme 22). Reaction optimization showed that use of benzonitrile as a cosolvent leads to cleaner and more efficient reactions. The functional group tolerance and chemoselectivity of the reaction simplified the protecting group strategy. 

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