Sequential 3-allyl-5-

The stereospecific construction of acycHc anti-1,3-carbon stereogenic centers and C2-symmetrical fragments was also accompHshed via the sequential allylic alkylation... 

Snieckus reported a combination directed ortho-metalation (DoM)-RCM strategy for the synthesis of benzazepine, benzazocine, and benzannulated sulfonamide heterocycles <00SL1294> (Scheme 60). For example, the Boc-protected aniline (75) was sequentially allylated to give 76 which underwent RCM in excellent yield to give benzazepine 77. Use of similar methodology led to 78 and 79 starting from Y-methylbenzamide and p-tolylsulfonamide, respectively. 

If 2,3-dibromo propene is used as an allylic substrate the substitution product 71 can be either isolated or, after addition of additives and adjustment of the reaction conditions, 71 can readily react in cross-coupling reactions with alkynes (Sonogashira coupling), stannanes (Stille coupling), or boronic acids and boronates (Suzuki coupling) to provide the sequential allylic substitution-cross-coupling products 72-78 in moderate to good yields (Scheme 23). 

Sequential allylic substitutions have also been used in an intermolecular-intramolecular fashion with 1,4-diacetoxy ds-2-butene 85 as a module, as shown by Hayashi and coworkers [81], to deliver morpholines 86 and piperazines with enantioselectivities up to 61% ee if a chiral chelating bisphos-phane such as BINAP is applied as a ligand (Scheme 26). 

Sequential allylic substitution-Stille coupling" Sequential allylic substitution-Suzuki coupling"... 

Scheme 23 Sequential allylic substitution-cross-coupling [80]...

The Heck reaction may also proceed in an intramolecular fashion if the aryl halide is covalently bound to the allyl substrate. In this case the sequential allylic substitution-Heck-cyclization with Pd acetate as a catalyst takes place very smoothly as an unimolecular process and furnishes the polycon-densed pyrrolidones 91 in excellent yields (Scheme 29). 

Intramolecular nucleophilic attack has been demonstrated in several cases, particularly with amine and (rj -allyl)Fp complexes an example of the former is depicted (equation 20). In such cases, the driving force for formation of five- or six-membered rings overrides the preference for attack at the more substituted alkene center. The ability of trialky-lamines to convert (> -aIkene)Fp+ complexes into (rj -allyl)Fp complexes via deprotonation allows conversion of alkadiene complexes (see Diene Complexes) (96) into carbocycles (97,98). The reasons for the stereochemical outcome of these cyclization reactions have not been fully delineated. Finally, ( ) -butadiene)Fp+ cations react in two sequential ( ) -allyl)Fp-( -alkene)Fp+ pairs to give a mixture of cyclic... 

Sequential allylic substitution-Sonogashira coupling "butyl ntjutyl... 

Hydronaphthacenes and benzofluorenes can be elaborated in one step, based on sequential allylic substitution and Heck reaction. 

For a hetero-Claisen rearrangement of allyl xanthate in the synthesis of agelasidine A see ref 369. Two sequential allyl xanthate rearrangements are described in ref 370. 

Scheme 1.8 Sequential allylic alkylation and Pauson-Khand reactions, both catalyzed by Co and PdNPs supported on silica for one-pot syntheses of bicyclic enones (Ref J5c, Chung group, Org. Lett. 2002, 4, 4J61).

Racemic validatol (7) and deoxyvalidatol (8) have been synthesized by the procedure outlined in Scheme 3 Racemic cyclitols have also been prepared from cyclohexene by repeated sequential allylic bromination and treatment with sodium benzyloxide to give a mixture of di(benzyloxy)cyclohexenes the 3,4-diether (9) then being hydroxylated by standard procedures leading to the tetraol derivatives (10) (the 1,2,4/3-, 1,3/2,4-, and 1,4/2,3-isomers), from which racemic dihydroconduritols could be obtained. ... 

A stereocontrolled synthesis of polyfused ring systems utilizing the chloroacet-oxylation approach is shown in Scheme 11.30 [106]. The use of sequential allylic substitution of the chloroacetates afforded the key intermediate 85. Subsequent palladium-catalyzed sequential metalloene-Heck insertion reactions afforded polyfused ring systems 86 and 87. 

One of the traditional methods for applications of the aliphatic Claisen rearrangement has used Mercuric salts to prepare vinyl ether as illustrated in the use of the allylic alcohol (28) en route to aldehyde 29. The chemical development group at Boehringer-Ingelheim has developd a mild palladium acetate-phenanthroline catalyst 31 for the sequential allyl vinyl ether-Claisen process utilizing commercially available triethyleneglycol divinyl ether which avoids the use of mercuric acetate. ... 

Biosynthesis of the sesquiterpene antibiotic albaflavenone in Streptomyces codicolor A3(2) was studied in detail. The mechanism and stereochemistry of the enzymatic formation of epi-isozizaene by multistep cyclization of famesyl diphosphate was investigated [101] and a P450 (CYP170A1) was identified to carry out two sequential allylic oxidations to convert epi-isozizaene to an epimeric mixture of albaflavenols and thence to albaflavenone [102],... 

SCHEME 3.22 Sequential allylic C—H amination/vinylic arylation. 

Homillos V, van Zijl AW, Feringa BL (2012) Catalytic asymmetric synthesis of chromenes and tetrahydroquinolines via sequential allylic alkylation and intramolecular Heck coupling. Chem Commun 48 3712-3714... 

Scheme 232 Sequential allylic amidation and atom-transfer radical cyclization.

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