Reductive allylation reactions

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

The allylation reaction can be adapted to the synthesis of terminal dienes by using l-bromo-3-iodopropene and stannous chloride. The elimination step is a reductive elimination of the type discussed in Section 5.8. Excess stannous chloride acts as the reducing agent. 

Dienes incorporated in a cyclohexane skeleton show different reaction features from acyclic dienes. Under the reductive allylation conditions, o> (2,4-cyclohexadienyl)alkanals 15 react to provide a homoallylation product 16a (n = 1) as a major product or 16a (n = 2) exclusively (Eq. 7) [ 19]. The expected allylation product is obtained as a minor product only for the reaction of 15 (n = 1). 

The prime functional group for constructing C-C bonds may be the carbonyl group, functioning as either an electrophile (Eq. 1) or via its enolate derivative as a nucleophile (Eqs. 2 and 3). The objective of this chapter is to survey the issue of asymmetric inductions involving the reaction between enolates derived from carbonyl compounds and alkyl halide electrophiles. The addition of a nucleophile toward a carbonyl group, especially in the catalytic manner, is presented as well. Asymmetric aldol reactions and the related allylation reactions (Eq. 3) are the topics of Chapter 3. Reduction of carbonyl groups is discussed in Chapter 4. 

The retrosynthesis involves the following transformations i) isomerisation of the endocyclic doble bond to the exo position ii) substitution of the terminal methylene group by a more stable carbonyl group (retro-Wittig reaction) iii) nucleophilic retro-Michael addition iv) reductive allylic rearrangement v) dealkylation of tertiary alcohol vi) homolytic cleavage and functionalisation vii) dehydroiodination viii) conversion of ethynyl ketone to carboxylic acid derivative ix) homolytic cleavage and functionalisation x) 3-bromo-debutylation xi) conversion of vinyl trimethylstannane to methyl 2-oxocyclopentanecarboxylate (67). 

Use of thiaprolinol amino alcohols as ligands for enantioselective borane reduction of ketones111 and of a fluorotitanium-TADDOLate to catalyse reduction of benzaldehyde87c has been described above under Organometallics and Allylation Reactions, respectively. 

Cross-coupling of allylic compounds occurs by transmetallation between 7i-allyl intermediates and organometallic compounds of Mg, Zn, B, Al, Si and Sn, and subsequent reductive elimination. Reaction of the allylic dithioacetal 180 with MeMgBr in the presence of an Ni catalyst affords alkenes 184 bearing a tert-butyl group [90]. In this reaction, generation of the 7i-allylnickel 181 by oxidative addition and subsequent transmetallation with MeMgBr afford 182. Then the methylated product 183 is formed by reductive elimination, and finally the dimethylated product 184 is formed by the sequence of similar reactions. 

Standard techniques are used to substitute on nitrogen. Allyl and substituted allyl halides substitute directly, whereas alkyl and CPM functions are best introduced via the acyl halide followed by LAH reduction.(61) Reaction of norbenzomorphans with N-nitrourea or with urea, acetic acid, and HC1 affords N-carbamoylbenzomorphans.(65,66) N-Arylamidinobenzomorphans have also been reported.(67)... 

Epoxy-l-haloalkenes undergo novel reductive cleavage reactions with samarium diiodide to give cyclopropanols or allylic alcohols depending upon the substrates and reaction conditions. Formation of the cyclopropanol is believed to proceed through a diradical intermediate <1998SL1073>. 

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