Cascade transmetallation

Cascading Transmetalations and Negishi Cross-Coupling Used in the Synthesis of p-Carotene... 

A tandem enolate-arylation-allylic cyclisation, in which an essential z-butyldimethylsilyl ether protecting group delays the cyclisation step until the Pd-catalysed arylation is complete, enables 1-vinyl-l//-[2]benzopyrans 54 to be prepared from 2-bromobenzaldehyde (Scheme 32) <00CC1675>. 4-Substituted isochromans 55 are formed from aldehydes by a Pd-catalysed termolecular queuing cascade. The sequence involves cyclisation of an aryl iodide onto a proximate alkyne followed by an allene insertion. Transmetallation with indium then allows addition to the aldehyde (Scheme 33) . 

Many pyridine-indole compounds are biologically active. A growing number of methods for the preparation of indolylstannanes have been developed. 2-Trialkylstannylindoles, for example, have been synthesized via directed metalation followed by reaction with tin chloride [91-93]. The latest indolylstannane syntheses include Fukuyama s free radical approach to 2-trialkylstannylindoles from novel isonitrile-alkenes [94], and its extension to an isonitrile-alkyne cascade [95]. Assisted by the chelating effect of the SEM group oxygen atom, direct metalation of 1-SEM-indole and transmetalation with BujSnCl afforded 2-(tributylstannyl)-l//-indole 108, which was then coupled with 2,6-dibromopyridine to give adduct 109. 

An improved procedure for cyclopalladation-carbonylation (of e.g. 320) relies on the addition of CuCl and LiCl to the standard PdCl2-CuCl2 mixture. This indicates that both the Cu2+ and Cu+ are required in sufficient concentrations to keep up the cascade of the catalytic cycle. This method is superior to the Hg(II)-mediated cyclization followed by transmetallation with Pd in CO/MeOH197. For application in the synthesis of polyether antibiotics, see elsewhere435. 

Cooper et al. reported that the cascade reaction of the palladium-catalyzed cyclization and the Barbier-type allylation of the 1,3-diene-aryl iodide 514, the aldehydes 515, and indium gave the heterocycles 516 in good yields (Scheme 154).220b The reaction proceeds through oxidative addition of a C—I bond of 514 to Pd(0) and subsequent insertion of a double bond of 517 to give the jr-allylpalladium intermediate 518. Transmetalation of the jr-allylpalladium 518 with indium leads to the allylindium complex 519, and the following reaction with the aldehydes 515 gives 516. 

The Pd-catalyzed cycUzation of alkenyl- and alkynyl-tethered allylic acetates gives a-alkyl- and alkenylpalladium intennediates, respectively, which can undergo further intramolecular alkene insertion, carbonylation, and transmetallation, respectively, to form additional carbon-carbon bonds (Scheme 8), as exemplified for such cascade reactions with insertion of a tethered alkene in Scheme 12.E3],[24H27]... 

Pd-catalysed bis-cyclization of l-ene-6,ll-diynes (19) with bis(pinacolato)diboron affords homoallylic alkylboronates (20), which indicates a cascade reaction, where the final transmetallation of bis(pinacolato)diboron is faster than a possible -hydride elimination process. ... 

Pd-catalysed bicyclizations of l-ene-6,ll-diynes with bis(pinacolato)diboron give homoallylic alkylboronates. One C B bond and two new C C bonds are created, and two new stereogenic centres are stereospecificaUy formed in a single tandem operation involving a cascade reaction in which the last step is the transmetalation of bis(pinacolato)diboron (Scheme 143). " ... 

Another intriguing cascade of an intramolecular Heck-type reaction followed by an intermolecular Stille coupling produces the dienyne 98 starting from the enyne 96 and the stannane 97 [322] (Scheme 8.25). The reversed sequence of a Stille-type reaction followed by a Heck reaction has also been applied. It is also possible to terminate such a sequence after transmetallation from a zincate [180a,c], either added to the reaction mixture [180a] or generated in situ from an iodoalkene [180c]. 

Allylpalladation of alkenes, alkynes, and dienes is a powerful tool for preparing carbocy-cles and heterocycles. The combination of aUylpalladations with intramolecular alkene insertion, carbonylation, and transmetallation in cascade-type sequences demonstrates the high potential of these Pd-catalyzed cyclization reactions for the synthesis of complex organic molecules. 

Two different metal-catalyzed cascade processes have also been reported. A recent example is the FeClj/PdClj-cocatalyzed coupling cyclization of 2,3-allenoates 41 with allylic bromides 42 (Scheme 5.25) [27], This protocol provides very concise access to P-allyUc-substituted butenolides 43. The key point for this catalyst relaying process is the in situ generation of sp carbon iron species A and its transmetallation with PdCl ... 

After investigation of the palladium-catalyzed cascade cyclization/Suzuki coupling reactions of 1,6-enynes, Zhu and Zhang turned their attention to the analog 1,2,7-triene 333 for the synthesis of various functionalized five-membered cycles 334/335 [115] (Scheme 6.88). Oxidative addition of allyl hahides or carbonates to Pd(0) generates 7i-allylpalladium species 336, followed by intramolecular cycUzation to form vinylpalladium complex 337. Subsequent transmetallation with aryl boronic acids... 

Recently, Lambert et al. reported on a new cascade of reactions incorporating palladium(II)-promoted oxycarbo-nylation of alkenyl alcohols. Intermediate cr-Pd(ll)-acyl species are transmetallated by a suitable organometallic reagent affording ketones or aldehydes (Scheme 15.25). 

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