Nucleophilic reactions allylations

Some nucleophiles other than carbon nucleophiles are allylated. Amines are good nucleophiles. Diethylamine is allylated with allyl alcohol[7]. Allylammes are formed by the reaction of allyl alcohol with ammonia by using dppb as a ligand. Di- and triallylamines are produced commercially from allyl alcohol and ammonia[l74]. 

Various S-nucleophiles are allylated. Allylic acetates or carbonates react with thiols or trimethylsilyl sulfide (353) to give the allylic sulfide 354[222], Allyl sulfides are prepared by Pd-catalyzed allylic rearrangement of the dithio-carbonate 355 with elimination of COS under mild conditions. The benzyl alkyl sulfide 357 can be prepared from the dithiocarbonate 356 at 65 C[223,224], The allyl aryl sufide 359 is prepared by the reaction of an allylic carbonate with the aromatic thiol 358 by use of dppb under neutral condi-tions[225]. The O-allyl phosphoro- or phosphonothionate 360 undergoes the thiono thiolo allylic rearrangement (from 0-allyl to S -allyl rearrangement) to afford 361 and 362 at 130 C[226],... 

The aziridine aldehyde 56 undergoes a facile Baylis-Hillman reaction with methyl or ethyl acrylate, acrylonitrile, methyl vinyl ketone, and vinyl sulfone [60]. The adducts 57 were obtained as mixtures of syn- and anfz-diastereomers. The synthetic utility of the Baylis-Hillman adducts was also investigated. With acetic anhydride in pyridine an SN2 -type substitution of the initially formed allylic acetate by an acetoxy group takes place to give product 58. Nucleophilic reactions of this product with, e. g., morpholine, thiol/Et3N, or sodium azide in DMSO resulted in an apparent displacement of the acetoxy group. Tentatively, this result may be explained by invoking the initial formation of an ionic intermediate 59, which is then followed by the reaction with the nucleophile as shown in Scheme 43. 

The protocol of the allylic alkylation, which proceeds most likely via a c-allyl-Fe-intermediate, could be further improved by replacing the phosphine ligand with an M-heterocyclic carbene (NHC) (Scheme 21) [66]. The addition of a ferf-butyl-substituted NHC ligand 86 allowed for full conversion in the exact stoichiometric reaction between allyl carbonate and pronucleophile. Various C-nucleophiles were allylated in good to excellent regioselectivities conserving the 71 bond geometry of enantiomerically enriched ( )- and (Z)-carbonates 87. Even chirality and prochirality transfer was observed (Scheme 21) [67]. 

Scheme 2.24 Whole catalytic cycle of frost s Mo-7t-allyl nucleophilic reaction.

Kondo and Watanabe developed allylations of various types of aldehydes and oximes by using nucleophilic (7r-allyl)ruthenium(ll) complexes of type 154 bearing carbon monoxide ligands (Equation (29)).345 These 73-allyl-ruthenium complexes 154 are ambiphilic reagents and the presence of the carbon monoxide ligands proved to be essential to achieve catalytic allylation reactions. Interestingly, these transformations occur with complete regioselectivity only the more substituted allylic terminus adds to the aldehyde. 

In addition to alkoxides, carbonyl oxygens have occasionally been recruited to function as nucleophiles in allylic etherification processes. The cyclization reactions of ketones containing internal allylic systems occur through O-allylation under Pd catalysis to give rise to vinyl dihydrofurans203 or vinyl dihydropyrans (Equation (51))204,205 in good yields. 

Sakai s elegant application of Pd-induced nucleophilic reactions of allylic acetates provides the first experimental support for the biogenesis of the koumine alkaloid skeleton and is an excellent concluding illustration of the power of palladium in indole chemistry. 

Allylic alkylation (cf., 12,557). This W(0) complex in combination with 2,2 -bipyridyl (bpy) catalyzes reactions of nucleophiles with allylic acetates or carbonates, but the chemoselectivity is complementary to that of Pd(0), as shown in equation (I). The W(0)-catalyzed reactions are influenced by inductive and steric... 

A useful extension of the in situ anomerization process involves the employment of C-nucleophiles such as vinyl and allyl magnesium bromides. Grignard reactions to per-O-benzylated glycosyl iodides proceed stereoselectively when a strong nucleophile like allyl magnesium bromide is used, giving [1-C-allyl fucosides (95% P-only)... 

Alkoxycarbenium ion pool 26 was allowed to react with allyltrimethylsilane as a carbon nucleophile to give the corresponding allylated product 27. The success of the nucleophilic reaction also indicated the presence of the alkoxycarbenium ion in relatively high concentration in the solution. 

Although Helmchen et al. showed that asymmetric iridium-catalyzed allylic substitution could be achieved, the scope of the reactions catalyzed by iridium complexes of the PHOX ligands was limited. Thus, they evaluated reactions catalyzed by complexes generated from [lr(COD)Cl]2 and the dimethylamine-derived phosphoramidite monophos (Scheme 8) [45,51]. Although selectivity for the branched isomer from addition of malonate nucleophiles to allylic acetates was excellent, the highest enantiomeric excess obtained was 86%. This enantiomeric excess was obtained from a reaction of racemic branched allylic acetate. The enantiomeric excess was lower when linear allylic acetates were used. This system catalyzed addition of the hthium salts of A-benzyl sulfonamides to aUylic acetates, but the product of the reaction between this reagent and an alkyl-substituted linear aUylic acetate was formed with an enantiomeric excess of 13%. 

The high concentration of ammonia that is required for selective formation of primary allylic amines suggests that ammonia is much less reactive toward nucleophilic attack on an allyl ligand than the primary allylic amine products. The reactivity of different nucleophiles toward allyl ligands was assessed by treating the allylir-idium complex 6a with ammonia and l-phenylprop-2-en-l-amine. No product from allylation of ammonia was detected from this reaction. In addition, the reaction of an allylic carbonate with the combination of ammonia and l-phenylprop-2-en-l-amine in the presence of lb did not produce detectable amounts of the product from allylation of ammonia. These results confirm that the primary amine is much more... 

The scope of reactions catalyzed by metalacychc iridium-phosphoramidite complexes is remarkably broad, but reactions with some substrates, such as allylic alcohols, prochiral nucleophiles, branched allylic esters, and highly substituted allylic esters, that would form synthetically valuable products or would lead to simpler symthesis of reactants occur with low yields and selectivities. In addition, iridium-catalyzed allylic substitution reactions are sensitive to air and water and must be conducted with dry solvents under an inert atmosphere. Several advances have helped to overcome some, but not aU of these challenges. 

Notes Ligand. Used for Pd-catalyzed nucleophilic reactions at allylic positions. See also, Dodd. With Br forms a useful brominating agent, l,2-bis(diphenylphosphino)ethane tetrabromide [7726-95-6],1 This reagent is useful for the conversion ... 

Interestingly, treating (>/4-cyclooctatetraene)Fe(CO)3 with acetyl chloride under Friedel-Crafts reaction conditions yielded unexpectedly222-223 the (>/2,>/3-8-e.x0-acetyl bicy-clo[3.2.1]octadienylium)Fe(CO)3 cation complex, presumably by rearrangement of the intermediate bicyclo[5.1.0]octadienylium isomer (Scheme 8). The structure of the rearranged cation was confirmed from the X-ray crystal structure and from the typical 1,3-cr.ji-allylic products obtained upon nucleophilic reaction with LiAlD4 and NaCN. The nucleophilic reaction of the more bulky iodide occurs, however, on the metal. 

Enantiomeric purity, palladacycle applications, 8, 295 Enantioselective addition reactions, nucleophiles to allylic... 

Both stoichiometric and catalytic reactions of allylic compounds via 7r-allyl complexes are known. Reactions of nucleophilic 71-allyl complexes with electrophiles involve oxidation of metals and hence constitutes stoichiometric reactions. 7i-Allyl complexes of Ni, Fe, Mo, Co and others are nucleophilic and undergo the stoichiometric reaction with electrophiles. However, electrophilic 71-allyl complexes react with nucleophiles, accompanying reduction of metals. For example, 71-allylnickel chloride (2) reacts with electrophiles such as aldehydes, generating Ni(II), and hence the reaction is stoichiometric. In contrast, electrophilic 7i-allylpalladium chloride (3) reacts with nucleophiles such as malonate and Pd(0) is generated. Thus repeated oxidative addition of allylic compounds to Pd(0) constitutes a catalytic reaction. 

However, reactions of 160 and 161 with methyl 2,2-bisdeuterioacetoacetate (164) give the products deuterated at different carbons namely 2-deuterio-3-hydrofuran 166 is obtained from 160 via 165. Also, reaction of 161 with 164 affords the furan 168, deuterated at the exomethylene carbon via 167. These results are explained by assuming that the attack by the oxygen nucleophile (O-allylation) occurs at the more substituted side of 7c-allylpalladium systems in 165 and 167. 

The second approach for the nucleophilic animation reactions to be considered here will be reactions of allyl halides and allyl acetates leading to allyl amines. Allyl halides are normally very reactive in SN2 reactions, but the direct coupling of allyl halides with nitrogen nucleophiles has been performed with limited success [4], as di- and trialkylated by products often predominate. The application of the Gabriel synthesis can to a certain extent eliminate the problem with polyalkylation of amines using, e.g., the stabilized phthalimide anion 19 as the nucleophile. The allyl amine 20... 

Allylic amination of allyl halides can also be achieved using lithium and potassium bis(trimethylsilyl)amides [34] and potassium 1,1,3,3-tetramethyldisilazide [35] as the nucleophiles. It has been found that for the reaction of alkyl-substituted allyl chlorides using lithium bis(trimethylsilyl)amides as the nucleophile the allylic amination proceeds smoothly in a SN2 fashion to give /V,Af-disilylamines in high yields when silver(I) iodide was used as an additive. Other metal complexes such as copper ) iodide and other silver(I) salts can also be used as additives for the reaction. 

---