Allylamines transformation reactions

Isomerization is a frequent side-reaction of catalytic transformations of olefins, however, it can be a very useful synthetic method, as well. One of the best-known examples is the enantioselective allylamine enamine isomerization catalyzed by [Rh (jR)-or(S)-BINAP (COD)] which is the crucial step in the industrial synthesis of L-menthol by Takasago [42]... 

Dihydromuscimol (49) is a conformationally restricted analogue of the physiologically important neurotransmitter y-aminobutyric acid (GABA) and has been prepared using the cycloaddition of dibromoformaldoxime to A-Boc-allylamine followed by N-deprotection with sodium hydroxide (Scheme 6.52) (278). The individual enantiomers of dihydromuscimol were obtained by reaction of the bromonitrile oxide with (5)-( + )-l,2-0-isopropylidene-3-butene-l,2-diol, followed by separation of the diastereoisomeric mixture (erythro/threo 76 24), hydrolysis of respective isomers, and transformation of the glycol moiety into an amino group (279). 

A combinatorial approach was applied to evaluate various catalysts for the animation of 1,3-dienes.594 Complexes formed from [(T 3-C3H5)PdCl]2 and PPh3 were the most active to induce the reaction of a broad range of primary and secondary ary-laminesand 1,3-cyclohexadiene, 1,3-cycloheptadiene, or 2,3-dimetyl-1,3-butadiene to give allylamines. The enantioselective version of the transformation is also very effective ... 

Recently it has been reported that the catalytic isomerization of allylic alcohols is promoted by [Rh(diphosphine)(solvent)2]+ at 25°C yields synthetically useful quantities of the corresponding simple enols and that the transformation of allylic alcohols to enols and thereby to ketonic products proceeds catalytically via hydrido-7t-allylic and hydrido-7t-oxy-allylic intermediates, respectively [20]. Consistently observed, enantioselection has been in the process of conversion of a prochiral enol to a chiral aldehyde. Thus, the prochiral substrate 32 is transformed to the optically active aldehyde 34 with 18% ee by using [Rh(BINAP)]+ catalyst (eq 3.13). Accordingly, this isomerization proceeds via a different mechanism from that of the isomerization of allylamine. For the reaction mechanism of the... 

The products of these reactions are easily transformed into allylamines by sequential treatment with (Me3Si)2NH and KOH. Quatemization of the nitrogen of 1.25, followed by reaction with PhMgBr at -78°C, gives sulfoxides 8.4 with an excellent enantiomeric excess. In turn, these sulfoxides undergo [2,3] sigmatropic transposition to allyl alcohols 8.5. In the ene reactions of 1.24, the enophile approaches the face of the N=S double bond opposite to the phenyl substituent of the auxiliary so that the A (1,3) strain is minimized (Figure 8.2). 

A related cyclization was recently reported by Jia et al. [14] with allylamine 20 immobilized on poly styrene-Wang resin. The reaction was monitored by acetylation and cleavage to yield 21, as a mixture of free and Boc-protected amines. This solid-phase synthesis of. seco-CBI (21, R = H), related to the pharmacophore of the CC-1065 and duocarmycin class of cyclopropylindole antitumor antibiotics, has potential for the preparation of analogue libraries, and an example of further transformation of resin-bound 21 to a polyamide was presented. 

The effect of the solvent on the product selectivity for the rhodium-catalyzed cyclization of an allylamine under a CO/H2 atmosphere (Scheme 70) is such that carbonylation in conventional organic solvents forms a cyclic amide 41, whereas the reaction in SCCO2 preferentially produces reduced five-membered cyclic amine 40. In SCCO2, the amino group of the starting material is transformed to the carbamic... 

The enantioselective C-silylation of allylic substrates such as (V-(terf-butoxycarbonyl)-A(-(p-methoxyphenyl)allylamines or 1,3-diphenylpropene is accomplished with butyUithium in the presence of (—)-sparteine, followed by the addition of TMSOTf (eq 47). The same procedure allows the asymmetric deprotonation-substitution of arenetricarbonyl(O) complexes, while chiral bis(oxazolines) have been the ligands of choice to perform such transformation with aryl benzyl sulfides in these reactions, different yields and enantioselectivities are reached if trimethylsilyl chloride is used as sUylating reagent, although there is a substrate dependence and no definite rules can be established. 

Later, Shaw and co-workers further employed sugar derived aldehydes 312 as electrophiles in the chalcogeno-MBH reaction (Scheme 2.170). The resulting allyl chlorides 313 can be easily transformed into allylamines 314 via treatment with various amine (Et2NH, pyrrolidine, piperidine and piperazine derivatives) (Scheme 2.170). They also evaluated these allyl chlorides and allylamines for their biological activity and found that (Z)-keto allyl chlorides possess antimycobacterial activity. ... 

Ligand fine-tuning continues to provide an important possibility to alter the individual product formation in the aerobic aza-Wacker reaction. For example, Zhang could show that phenanthroHne also constitutes a suitable ligand for this type of reaction, surpassing the more common pyridine in the transformations of alkene 37 to allylamine 38 (Scheme 16.9). 

Due to the importance of indoles, Joergensen and co-worker reported a palladium-catalyzed amination, followed by a Heck reaction of 1,2-dihaloarenes in 2008. Various 3-substituted indoles were isolated in moderate to good yields by using allylamine as a coupling partner (Scheme 2.13). In their study, they showed that the first step for this transformation was C-N coupling and the intermediate was isolated as well. 

Allyl amines and alkynes were explored as starting materials for pyridines synthesis by Jun and coworkers as well [109]. The reaction proceeded through a sequential Cu(II)-promoted dehydrogenation of the allylamine and Rh(III)-catalyzed iV-annulation of the resulting a,/3-unsaturated imine and alkyne. Moderate to good yields of pyridines can be isolated (Scheme 3.52). This transformation was later on explored with ruthenium catalyst [110]. In the presence of [ RuCl2(p-cymene) 2] (0.1 equiv.), KPFe (0.1 equiv.), and Cu(OAc)2 (1 equiv.) in tAmOH at 100°C, the desired pyridine derivatives were formed in good yields. In this case, the reaction started with C-H activation and then insertion to alkynes which is different from the rhodium catalyzed case. 

As a special case, the formation of hemiacetals 2 (lactolization) during the hydroformylation of hydroxy-functionalized olefins, such as allyl or homoallyl alcohols, has to be mentioned (1, Y= O, Scheme 5.70). With these substrates, the reaction occurs in an intramolecular manner. In the presence of an external alcohol, the cyclic hemiacetal can further react to give a nonsymmetric cyclic acetal 3. Hemiacetals can be subjected to hydrogenation to afford diols 4. Under reducing conditions and in the presence of amines, amino alcohols 5 are formed both are valuable building blocks in fine chemistry. Alternatively, oxidation gives lactones 6 [5]. By dehydration of hemiacetals, cychc vinyl ethers 7 are formed. The same transformation with allylamines (Y=NR) gives cyclic hemiaminals, A/ ,0-acetals, lactames, or vinyl amines. 

C-C bond activation also occurs in reactions of allylamines. For example, allylamine 74 undergoes double bond isomerization to form the corresponding aldimine 75 under transition metal catalyzed conditions. In 75, C-H and C-C bonds exist a to the imine moiety and, as a result, activation of both of these bonds enables this substance to serve as a synthetic surrogate of formaldehyde (Scheme 13a). Accordingly, treatment of allylamine 74 and olefin 47 with a catalytic amount of rhodium catalyst (66/67) leads to formation of the symmetric dialkyl ketone 77 along with a small amount of ketone 76 (Scheme 13b) [31]. In this process, 74 is first transformed to the corresponding imine 75, which then... 

In the last few years, several groups have developed enantioselective domino reactions catalysed by combinations of organocatalysts with palladium complexes. As an example, Murkheqee and List have reported a domino synthesis of p-all earbon quaternary amines on the basis of a highly enantioseleetive a-allqrlation of a-branched aldehydes, involving an achiral palladium catalyst and a chiral phosphoric acid. Under the catalysis of phosphoric acid, a secondary allylamine reacted with an a-branehed aldehyde to form an enammonium phosphate salt, which upon reaction with palladium catalyst afforded a cationic 7t-allyl palladium complex (Scheme 7.2). This intermediate resulted in the formation of an a-allylated iminium ion, whieh eould be reduced to the corresponding final chiral amine in high yield and exeellent enantioselectivity of 97% ee. The synthetic utility of this transformation was also demonstrated hy a formal synthesis of (+)-cuparene. 

A new route from alkyl halides to the corresponding amines (as acyl derivatives) involves reaction with A-acyl allylamines (Scheme 34), and subsequent deallylation with Pd salts used catalytically. Palladium species also intervene in the conversion of optically active benzyl halides, with inversion at the original C-halogen bond, to acyl Pd complexes ie.g. 71 ->72) which may be further transformed to carboxylic esters as shown. Alkyl halides give unpredictable results in this sequence. A related conversion can be carried out under phase... 

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