Tandem allyl electrophile

Oxidative Heck reactions via Pd(II) C—H functionalization of terminal alkenes with pinacol boranes have been described for the preparation of styrenes and derivatives through electrophilic Pd(II) catalysis (Scheme 3.20). ° Treatment of a functionalized allylic precursor with the Pd(II) catalysts listed facilitated an allylic C—H activation. Subsequent transmetallation of the aryl boronic acid and reductive elimination afforded the desired olefin with excellent stereoselectivity. The scope of the transformation allows for a variety of activating and deactivating substituents on the aryl boronic acid as well as numerous functional groups on the starting alkene. A tandem allylic C—H oxidation/vinylic arylation protocol has also been reported. " ... 

The catalytic system copper/L19 gives moderate diastereoselectivities (see examples in Scheme 50) in a tandem CA electrophilic trapping process, using allyl, benzyl and propargyl halides as electrophiles. 

The tandem reaction of allyl electrophiles with alkynes and MejAl or Mc2Zn occurs in the presence of Ni(acac)2 to give a regioisomeric mixture of the three-component coupling products [234]. The reaction can also proceed intramolecu-larly to give cyclic nonconjugated dienes. 

Usually, after an enolate ion is generated from an ocP-unsaturated ketone, it is converted to the P-alkylated product as shown above. But it is often possible to have the enolate react with some other electrophile (tandem vicinal difunctionalization), in some cases at the O and in other cases at the C. For example, if an alkyl halide R X is present (R = primary alkyl or allylic), and the solvent is 1,2-dime-thoxyethane, the enolate (66) can be alkylated directly. Thus, by this method, both the a and p positions of a ketone are alkylated in one synthetic operation (see also 15-23). 

Scheme 3.24. Tandem insertion of allyl carbenoids and electrophiles into zirconacycles.

The tandem zirconocene-induced co-cyclization of dienes or enynes/insertion of allyl carbenoid/addition of electrophile is a powerful method for assembling organic structures. Two illustrations of its application are the synthesis of the dollabelane natural product acetoxyodontoschismenol 99 [57,62,63] and the one-pot construction of linear terpenoids 100 (Scheme 3.25) [59,64],... 

Furthermore, intercepting the furylpalladium(II) species 130 with an electrophile would result in a carbodepalladation in place of protodepalladation. Therefore, a tandem intramolecular alkoxylation of p.y-acetylenic ketone 127 was realized to afford trisubstituted furan 131 when allyl chloride was added to the original recipe [103]. 2,2-Dimethyloxirane was used as a proton scavenger, ensuring exclusive formation of 3-allylated 2,5-disubstituted furan 131 without contamination by protonated furans. 

Another type of Cinchona alkaloid catalyzed reactions that employs azodicarbo-xylates includes enantioselective allylic amination. Jprgensen [51-53] investigated the enantioselective electrophilic addition to aUyhc C-H bonds activated by a chiral Brpnsted base. Using Cinchona alkaloids, the first enantioselective, metal-free aUyhc amination was reported using alkylidene cyanoacetates with dialkyl azodi-carboxylates (Scheme 12). The product was further functionalized and used in subsequent tandem reactions to generate useful chiral building blocks (52, 53). Subsequent work was applied to other types of allylic nitriles in the addition to a,P-unsaturated aldehydes and P-substituted nitro-olefins (Scheme 13). 

Contrary to what is observed during tandem addition reactions to [Os]-toluene (vide supra), electrophilic additions to [Os]-bound ortho- and meta-xylenes result in regioselective attack at C6 (Table 3). A coordination isomer having the metal across C4-C5 (19) is the only isomer observed for both ortho- and meta-xylene. Electrophilic addition of HOTf (entry 1) or dime-thoxymethane (entries 2 and 3) at C6 generates the complexed allyl cation 20, which can be trapped with MMTP to form the complexed diene 21. Demetalation using AgOTf releases the free diene 22, which potentially possesses two adjacent quaternary centers (entry 3) [15]. 

An alternative mode of reactivity is observed for [Os]-naphthalene when the nucleophile for the tandem addition is built into the electrophile. The normal mode of reactivity results in the formation of cis-l,4-dihydronaphthalenes (vide supra), but when a solution of the methyl vinyl ketone Michael addition product 24 in methanol (Table 6, entry 1) and a catalytic amount of triflic acid are allowed to react, the complexed hydrophenanthrenone 25 is isolated in 89 % yield [18]. This reactivity results from the pendant ketone undergoing a tauto-merization to form an enol, which can then attack the allyl cation at C2. The stereochemistry of the nucleophilic addition is still anti to the face involved in the metal coordination, but the... 

The chiral anisole derivative 37 has been used in the synthesis of several asymmetric functionalized cyclohexenes (Table 9) [22]. In a reaction sequence similar to that employed with racemic anisole complexes, 37 adds an electrophile and a nucleophile across C4 and C3, respectively, to form the cyclohexadiene complex 38. The vinyl ether group of 38 can then be reduced by the tandem addition of a proton and hydride to C2 and Cl, respectively, affording the alkene complex 39. Direct oxidation of 39 liberates cydohexenes 40 and 41, in which the initial asymmetric auxiliary is still intact. Alternatively, the auxiliary may be cleaved under acidic conditions to afford /y3 -allyl complexes, which can be regioselectively attacked by another nucleophile at Cl. Oxidative decomplexation liberates the cyclohexenes 42-44. HPLC analysis revealed high ee values for the organic products isolated both with and without the initial asymmetric group. 

The addition of organolithiums to allylic alcohols followed by trapping of the intermediates by electrophiles is a good example of the usefulness of this type of carbolithiation. The sequence leads, generally, to the formation of diastereomeric alcohols, but the use of chiral ligands confers enantioselectivity to the tandem reaction. 

Tandem insertion of aUyl carbenoids and aldehydes affords some organic compounds resnlting from a three-component coupling reaction. The most extensively studied application of this methodology is the insertion of allyl carbenoids into zirconacycles and subsequent elaboration of the formed allylzirconocenes with electrophiles (Scheme 39). ... 

In Scheme 62 are shown recently developed cyclization reactions of iV-nucleophiles on olefmic electrophiles to give piperidines. In an iodolactamization method, chiral 154 gave 155 in 90% yield and 97% de. <04JOC7906>. A tandem Heck-allylic substitution reaction served to convert 156 to 157 with modest diastereoselectivity. A proposed intermediate is the ally lie palladium species 158 <04T9687>. An amidomercuration reaction of similar olefinic substrates to give 2,6-dialkylpiperidines has been reported <040L3067>. 

Acetylenic aldehydes 96 have been utilized as electrophiles in MBH reactions to give allyl propargyl alcohols 97 in moderate to good yields. Aldehydes 98, as a masked formybutadiene, react with activated olefins to give the eorre-sponding MBH adducts 99 via a tandem sequence base-induced elimination-MBH reaction catalyzed by DABCO (Seheme 1.47). ° ... 

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