Aminoalkenes

Although efficient for the intramolecular hydroamination/cyclization (abbreviated IH below) of aminoalkenes (see below), organolanthanides exhibit a much lower catalytic activity for the intermolecular hydroamination of aUcenes, as exemplified by the reaction of n-PrNH2 with 1-pentene catalyzed by a neodymium complex (Eq. 4.17) [127]. 

Scheme 4-3 Catalytic cycle for the organolanthanide-catalyzed IH of aminoalkenes...

IH of hindered aminoalkenes has been developed as a route to heterocycles containing quaternary centers a to the nitrogen atom (Eq. 4.21) [134]. For these reactions, the easy-to-prepare catalyst precursors [(MejSiCpljLnMejj prove very efficient. 

The IH of exocyclic alkenes allows the construction of bicyclic amines bearing one methyl group at the ring junction. Although long reaction times (2-7 days) are necessary (Eq. 4.22), amines are obtained in good yield. In contrast, endocyclic aminoalkenes are resistant to cyclization [134]. 

The above catalyst precursors have been used with success for the IH of several other hindered aminoalkenes, including 5-methylenecyclooctylamine (Eq. 4.23) [134]. 

These reactions (Eq. 4.86) are 10-100 times more rapid than the corresponding IH of primary aminoalkenes with the same catalyst. TOFs up to 7600 h have been observed (Cp 2SmCH(TMS)2, R = MejSi, n = 1) [303]. 

The ring-size dependence of the cyclization rate (TOE) is 5 > 6, as already observed for IH of aminoalkenes and aminoalkynes. 

With regard to TOE, the IH of aminoaUenes is significantly more rapid than that of the corresponding aminoalkenes, but slower (ca. 5-20 times) than that of the corresponding aminoalkynes. 

Scheme 10.80 Y-catalysed hydroaminations of aminoalkenes with binaphthylamine-derived dithiol ligand.

The bicyclic aminoalkene l-azabicyclo[4.4.4]tetradec-5-ene (32) behaves actually like an enamine96. It is oxidized more readily than its saturated analogues. Protonation does not occur on the nitrogen atom but at the double bond accompanied by transannular cyclization (32 — 33). 

In the difunctional aminoalkene 32 the nc=C MO is destabilized relative to that of alkene 35 by ca 0.5 eV while the n orbital is stabilized relative to that of amine 35 by the same amount. This is the largest n/ c=C interaction known so far. 

In the monocyclic aminoalkenes 36-39 with an exocyclic CC double bond, only for the eight-membered ring compounds 37 has sizeable un/ c=C interaction been detected by PES48,97. The through-space interaction of these orbitals in aminoalkenes was found to increase exponentially as their distance decreases97. 

The dehydrohalogenation of analogous bis(trifluoromethyl)amines 60, 62, and 64 with potassium hydroxide affords the bis(trifluoromethyl)aminoalkenes 61, 63, and 65.112113... 

Two papers discussing the reactions of azetidines follow. iV-Activated azetidines are converted into aminoalkenes in a regiospecific ring opening at the benzyl carbon when treated with allylsilanes and BF3OEt2 in dichloromethane (Scheme 19).56... 

Several neutral titanium complexes have been shown to catalyse intramolecular hydroamination reactions of alkenes. The corresponding pyrrolidine and piperidine products were formed in up to 97% yields. However, only the geminally disubstituted aminoalkenes were successfully cyclized (Thorpe-Ingold effect).56... 

A dimeric proline-derived diamidobinaphthyl dilithium salt has been introduced as the first example of a chiral main group metal-based catalyst for asymmetric hydroami-nation-cyclization reactions of aminoalkenes.256... 

Aminoalkenes, oxidative cyclization, 10, 710-711 Aminoalkoxides, on zinc compounds, 2, 371 a-Aminoalkylallenes, cycloisomerizations, 10, 720 a-Aminoalkylcuprates, preparation, 9, 519-520 -Aminoalkylidynes, diiron carbonyl complexes with cyclopentadienyl ligands, 6, 248 Aminoalkynes, hydroamination, 10, 717 a-Aminoallenes, activation by gold, 9, 574 Amino r]5-amides, in Ru and Os half-sandwich rf3-arenes,... 

Intramolecular hydroamination of aminoalkenes CH2=CH(CH2) CH2NH2 and the corresponding alkynes can be catalysed by the calcium /9-diketiminato complex [ HC (C(Me)2N-2,6-Pr2C6H3)2 Ca N(SiMe3)2 (THF)] to produce the corresponding pyrrolidines and piperidines.71... 

Platinum-catalysed intramolecular hydroamination of unactivated alkenes with secondary alkylamines has been reported. Thus, a number of y- and 5-aminoalkenes reacted in the presence of a catalytic 1 2 mixture of [PtCl2(H2C=CH2)]2 (2.5 mol%) and PPh3 in dioxane at 120 °C for 16 h to form the corresponding pyrrolidine derivatives in moderate to good yields. The reaction displayed excellent functional group compatibility and low moisture sensitivity.92... 

Cazes et al. reported the Pd-catalyzed intermolecular hydroamination of substituted allenes using aliphatic amines in the presence of triethylammonium iodide leading to allylic amines [19]. In a way similar to the Pd-catalyzed hydrocarbona-tion reactions we reported that the hydroamination of allenes [20], enynes [21], methylenecyclopropanes [22], and cyclopropene [10] proceeds most probably via oxidative addition of an N-H bond under neutral or acidic conditions to give allylic amines. The presence of benzoic acid as an additive promotes the Pd-medi-ated inter- and intramolecular hydroamination of internal alkynes [23]. Intramolecular hydroamination has attracted more attention in recent years, because of its importance in the synthesis of a variety of nitrogen-containing heterocycles found in many biologically important compounds. The metal-catalyzed intramolecular hydroamination/cyclization of aminoalkenes, aminodienes, aminoallenes, and aminoalkynes has been abundantly documented [23]. 

Insofar as asymmetric synthesis is concerned, some pioneering work was conducted by Marks and co-workers through their demonstration of enantioselectivity in the samarium or lanthanide complex-catalyzed cyclization of aminoalkenes, an analogy of the simple reaction exemplified in Scheme 36. As before, the reaction works best for Se-unsaturated amines where the product of an exocyclic ring closure pathway is a cyclopentylamine. In the most favorable cases, high turnover to the desired product is observed [110] (Scheme 37). 

Intramolecular addition of amine N-H bonds to carbon-carbon multiple bonds would afford nitrogen heterocycles. To realize catalytic cyclization of a,co-aminoalkenes or aminoalkynes, various catalytic systems have been developed especially with early transition metals such as titanium, zirconium, lanthanide metals, and actinide metals [ 12], Late-transition-metal catalysis based on Ni, Pd, and Rh has also proved to be efficient [ 12], Recently, the ruthenium-catalyzed intramolecular hydroamination of aminoalkynes 15 was reported to afford 5-7-membered ring products 16 in various yields (Eq. 6) [13]. Among... 

Similar cyclic imines can be synthesized by intramolecular oxidative amination of aminoalkenes, which are less expensive than aminoalkynes. In the presence of catalytic amounts of [RuCl2(CO)3]2/l,3-bis(diphenylphosphino)propane and excess K2C03/allyl acetate, various aminoalkenes 19 possessing substituent(s) f3 to the amino group afforded five- and six-membered cyclic imines 20 in mod-erate-to-excellent yields (Eq. 8) [14]. 

Except in a few cases,cyclic Mannich ba.scs derived from alkenes arc produced by the reaction of unsaturated amino derivatives with formaldehyde. Intramolecular aminomethylation (Fig. 65) takes place with aminoalkenes (184, X = H path a) or with analogous silyl allyl derivatives (184, X = SiMc , path b) ... 

Hg. 167. Synthesis of aconitine-type diterpene alkaloids by intramolecular aminomethyla-tioii leading to a P-aminoalkene (bold lines) derivative. 

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