Allylic alkylation intermolecular

The final modes of enantioselective allyl alkylations catalyzed by palladium involve the use of chiral nucleophiles447 and chiral leaving groups.448-449 Chiral enamines were found to undergo allylation in 100% optical yield in an intramolecular case and in up to 50% optical yield in intermolecular reactions (equation 358). 

Direct catalytic intermolecular a-allylic alkylation of aldehydes and cyclic ketones has been achieved using a one-pot combination of a transition metal catalyst, Pd(PPh3)4, and an organocatalyst a secondary amine which facilitates enamine catalysis.300... 

A simple method for the direct catalytic allylic alkylation of aldehydes and cyclic ketones has been developed.26 The direct catalytic highly chemo- and regio-selective intermolecular a-allyhc alkylation reaction has been mediated by an unprecedented combination of palladium and enamine catalysis which furnishes a-allylic alkylated aldehydes and cyclic ketones in high yield. 

Scheme 12 Pd-catalyzed intra- and intermolecular allylic alkylation...

Scheme 29 Palladmm(II)-catalyzed intermolecular oxidative allylic alkylation...

White and co-workers also reported an intermolecular oxidative allylic alkylation reaction using a similar palladium(II) complex 50 (Scheme 29) [52]. 

Palladium Catalysts Palladium catalysts are effective and powerful for C—H bond functionalization. Carbene precursors and directing groups are commonly used strategies. Generally, sp3 C—H bond activation is more difficult than sp2 C—H bond activation due to instability of potential alkylpalladium intermediates. By choosing specific substrates, such as these with allylic C—H bonds, palladium catalytic systems have been successful. Both intramolecular and intermolecular allylic alkylation have been developed (Scheme 11.3) [18]. This methodology has presented another alternative way to achieve the traditional Tsuji-Trost reactions. 

A rapid and eflEcient molybdenum-catalyzed, MW-accelerated asymmetric allylic alkylation under noninert conditions has been reported [226]. Intermolecular hydroacylation of 1-alkenes with aldehydes has been presented as a greener alternative to the classical approach using a homogeneous catalyst in toluene. 

Scheme 4 Catalytic intermolecular a-allylic alkylation of cyclohexanraie...

The rhodium-catalyzed [5-1-2] cycloadditions have been used in cascade with other processes to synthesize molecules of more complexity in a single operation. The first example was reported by Martin who developed a cascade sequence involving allylic alkylation and [5-1-2] cycloaddition (see (20)) [42,43]. The catalyst [Rh(CO)2Cl]2 could be used to catalyze both the highly regioselective allylic alkylation and the following intramolecular [5-1-2] cycloaddition. As another example, Wender and co-workers combined intermolecular [5-1-2] cycloaddition with... 

In 2009, Kemmerer et al. uncovered a phosphine-free carbopalladation/allylic alkylation cascade sequence for the synthesis of 4-(a-styryl) y-lactams 308 [106] (Scheme 6.79). The reaction pathway of this transformation involves the formation of Jt-allylpalladium(n) species 307, which was trapped by the intermolecular active methylene. Both electron-rich and electron-deficient aryl iodides could be introduced efficiently to this cascade process. Li and Dixon developed a stereoselective and efficient protocol for the synthesis of spirolactam 310 employing a similar carbopalladation/jt-allylpalladium trapping strategy [107] (Scheme 6.80). 

By an analogous route, the cyclization of chiral (z-amino imines 197, bearing the proper tw-functionality in the o -alkyl chain, will lead to 3-substituted 1,2-diaminocycloalkanes 198. The intermolecular and intramolecular addition of allylic silicon and tin compounds to a-amino azomethine compounds should also be investigated. 

In conclusion, it appears that allyl or polyenyl radicals are much less reactive than alkyl radicals, which restricts the use of polyenes in intermolecular radical chain reactions to simple two-step processes. Allyl radicals are, however, reactive enough to partake in a variety of intramolecular reactions. 

Double alkylation of ( + )-(3/ )-ll [ ]d6 25.9 (c = 0.61, CHC13) ca. 93% ee with the dibromo compound 14, i.e., first an intermolecular alkylation by an allylic bromide, followed by an intramolecular alkylation with a homoallylic bromide, yielded (-)-15 in 54% yield and with very high diastereoselectivity60. The reaction is carried out in one pot with addition of the base, in this case potassium hexamethyldisilazanide (KHMDS), in two portions. 

The thermal rearrangement of allyl ethers is a process entirely different from. the rearrangement of saturated alkyl phenyl ethers by acidic catalysts.103 The latter process seems to be intermolecular, gives consider-... 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

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