Allylamines synthesis

An enantioselective version of this allylamine synthesis employs the chiral (S,S)-dimethylzirconium derivative 3, prepared from (S,S)-[l,2-ethylenebis(tetrahydro-l-indenyl]zirconium dichloride.3 Displacement of one methyl group by triflic acid followed by reaction with a lithium anilide results in a zirconaaziridine (a) with loss of methane. Reaction of a with a symmetrical alkyne provides a metallapyrroline (b), which is hydrolyzed to an (S)-allylamine (4) in 90-99% ee. The method tolerates variation in the lithium anilide. Terminal alkynes do not react with a, but 1-trimeth-... 

S. Otsuka, K. Tani, Catalytic Asymmetric Hydrogen Migration of Allylamines, Synthesis 1991, 665-680. 

SCHWARTZ Hydrolirconation 339 SCHWEIZER Allylamine synthesis 340 SCHWEIZER Rearrangement 341 Semidina 434... 

Pyrrohdinone (2-pyrrohdone, butyrolactam or 2-Pyrol) (27) was first reported in 1889 as a product of the dehydration of 4-aminobutanoic acid (49). The synthesis used for commercial manufacture, ie, condensation of butyrolactone with ammonia at high temperatures, was first described in 1936 (50). Other synthetic routes include carbon monoxide insertion into allylamine (51,52), hydrolytic hydrogenation of succinonitnle (53,54), and hydrogenation of ammoniacal solutions of maleic or succinic acids (55—57). Properties of 2-pyrrohdinone are Hsted in Table 2. 2-Pyrrohdinone is completely miscible with water, lower alcohols, lower ketones, ether, ethyl acetate, chloroform, and benzene. It is soluble to ca 1 wt % in aUphatic hydrocarbons. 

Synthesis of E allylamines from vinylphosphomum saRs and aldehydes (via WRtig reaction)... 

The benzodiazepine nucleus is extremely important, as it is the base of several drugs and other biologically active compounds with different properties. A facile synthesis of 2-methyl-l,4-benzodiazepin-5-ones has been described by Santagada and co-workers [162]. Isatoic anhydride 254 was reacted with M-substituted allylamines under microwave irradiation to give compound 255... 

In the synthesis of N heterocycles, this technique also overcomes competitive retro Michael addition that lowers the yield of 1,4-adduct in the Michael addition of amines to nitro olefins. Thus, a toluene solution of nitro olefin 159 was treated with allylamine 160, EtgN, and TMSCI under nitrogen at ambient tern-... 

An intramolecular nitrone 1,3-dipolar cycloaddition reaction to give 46 from 45 followed by reductive N-O bond cleavage afforded a stereoselective synthesis of the tetrahydro 177-1-benzazepines 47 the nitrone precursors 44 were prepared in turn by a Claisen rearrangement from an IV-allylamine <06SL2275>. 

Cycloaddition of nitrone (26) to allylamine (538) leads to the synthesis of chiral tetracyclic isoxazolidine (539) which is used in the preparation of compound R107500. This compound has been found to be active as an antiolytic and antidepressant. It also has the potential to inhibit drug abuse (Scheme 2.252) (80). 

The synthesis of a variety of chiral aliphatic aldehydes of high optical purity through the enantioselective isomerization of allylamines found many applications in organic synthesis. The enantioselective isomerization of diethylgeranylamine, which was prepared from myrcene, furnished (R, )-diethylenamine in >98% yield with >98% ee. This enamine is converted to (—(-menthol stereospecifically in high chemical yield (yield of each step >92%, Scheme 4).9 11... 

Metal-catalyzed C-H bond formation through isomerization, especially asymmetric variant of that, is highly useful in organic synthesis. The most successful example is no doubt the enantioselective isomerization of allylamines catalyzed by Rh(i)/TolBINAP complex, which was applied to the industrial synthesis of (—)-menthol. A highly enantioselective isomerization of allylic alcohols was also developed using Rh(l)/phosphaferrocene complex. Despite these successful examples, an enantioselective isomerization of unfunctionalized alkenes and metal-catalyzed isomerization of acetylenic triple bonds has not been extensively studied. Future developments of new catalysts and ligands for these reactions will enhance the synthetic utility of the metal-catalyzed isomerization reaction. 

Similar results were obtained for the synthesis of azapolycycles having relatively rigid skeletal frameworks. Thus, refluxing of TV-substituted TV-allylamines 163 under conditions of high dilution in xylene gave the cycloadducts 164 in 67% yield along with the products of hydrogen shift 165 and 166 (equation 50)67. 

The synthesis of menthol is given in the reaction scheme, Figure 5. 6. The key reaction [2] is the enantioselective isomerisation of the allylamine to the asymmetric enamine. It is proposed that this reaction proceeds via an allylic intermediate, but it is not known whether the allyl formation is accompanied by a base-mediated proton abstraction or hydride formation. 

Sonochemical methods have been used by the Cordoba de Torresi group to prepare Ni(OH)2, Co(OH)2 and mixed Ni/Co hydroxide NPs [33, 34]. For the sonochemical synthesis, the appropriate metal nitrate was mixed with ammonium hydroxide solutions and then sonochemically irradiated for various times. This produced about 5-nm diameter metal-hydroxide NPs that were then immobilized at ITO surfaces using a LbL approach with poly(allylamine) hydrochloride (PAH). In one study, the electrochromic behavior of the LbL deposits was compared with that of bulk deposits... 

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]... 

Unprotected branched allylamines are interesting chiral building blocks in organic synthesis (cf Section 9.6). The removal of N-benzyl- and related protecting groups... 

In work like that described in Scheme 6, Bruening reported the synthesis of multilayer composites by alternating deposition of Gantrez and the linear polyvalent nucleophile poly(allylamine) [58]. The impermeable films that were produced by this multistep hyperbranched graft chemistry were shown to passivate aluminum surfaces. 

Fluconazole and itraconazole are newer, orally effective triazole derivatives. The topically active allylamine naftidine and the morpholine amorolfine also inhibit ergosterol synthesis, albeit at another step. 

Further functionalization at OH-2 was also explored [187]. From monosacchari-dic (ot-gluco, 129) and disaccharidic (a-malto, 143) CMGLs, several types of bisfunctionalized systems were synthesized by reaction with allylamine or propar-gylamine. For example, compound 155 was prepared and used in a synthesis of the nucleotide sugar analog 156 (Scheme 38). In the context of studies on the... 

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