N-Allylic enamines

Nitrogen compounds have also been used in aza-CIaisen rearrangement reactions (also see the aza-Cope rearrangement in sec. 11.12.C.iii). 33,478 jn jie generic reaction, heating N-allylic enamines leads to an imine, which could be hydrolyzed to an aldehyde or converted to another nitrogen-containing moiety. 

The 3-aza Cope rearrangement of N-allyl enamines is mediated by Pd(PPh3),/-CF3C00H, while Pd(0), Pd(II), Rh(I) and Ir(I) complexes effect the closely related conversion of allyl imidates Into allylic amides (eqn.24). The Isomerisation of allylic alcohols under oxidative conditions is catalysed by V(0)(acaC)2 or Mo02(acac)2 and can be temperature dependent (eqn.25). ... 

The reactions of tertiary allylic amines with vinylic halides are related closely to the allylic alcohol reactions since enamines are often major products. We have just begun work in this area and have few results to report yet. We have seen some significant differences in the products formed from tertiary allylic amines and from the related allylic alcohols. A typical example is the reaction of 2-bromopropene with N-allyl piperidine and piperdine where a 42% yield of a single enamine is obtained (6). The related reaction with allyl alcohol gives a mixture of regioisomeric enamines. 

Photochemical Fe(CO)5-induced rearrangement of silylated allyl amine 9 gave N-silylated enamine 1015, which on subsequent Cu-catalyzed cyclopropanation by methyl diazoacetate afforded cyclopropane derivative 11. The use of an optically active catalyst gave an asymmetric induction of 56% ee for the cis isomer and 20% ee for the trans isomer. Further acid-induced ring cleavage afforded the -formyl ester 12, whereas reduction and desilylation produced aminocyclopropane carboxylic acid 13 (equation 2). 

Any mechanistic proposal should accommodate the results, (1) 1002 1,3-hydrogen migration and (2) 1002 trans-enamine formation. We postulate an n-allyl-hydride Rh(III) complex as the reactive intermediate as it accommodates these features and is consistent with other observations, viz., (1) faster rate for E- than for... 

Stille and co-worker developed an attractive route to aza-Claisen precursors. Allylamine reacted with 2-methylpropanal (isobutyraldehyde), for example, to give allylimine 658. When this reacted with 2-methylpropanoyl chloride, N-acyl derivative 659 was produced (94% overall yield from allylamine) and reduction with LiAlH4 give a 98% yield of the tertiary amine, 660. Stille found that conversion of the amine to the ammonium salt by treatment with HCl led to clean conversion to 661 in 82% yield via a [3,3]-sigmatropic rearrangement (an aza-Claisen rearrangement). Reduction of the iminium salt led to an 81% yield of 662 from 661. Stille and co-workers also found that Lewis acids as well as HCl react with the allyl enamine precursor to facilitate the aza-Claisen rearrangement. 2... 

N-Allyl difluoro enamines 77 suffered from a rearrangement 2-t2 cycloaddition domino process upon heating to about 140 °C. The effectiveness of final cycloaddition (79) strongly depended on the buUdness of R Sterically encumbered substituents R (CPh20SiMe3) supported the rearrangement (78). In contrast, a small R (SiMcj, Ph) led to substantial amounts of the cycloadduct 79 (Scheme 10.19) [15f]. 

A domino process of enamine 136 formation, N-allylation, aza-Claisen rearrangement and a final Mannich condensation was introduced by Florent [22g]. Aldehyde 135 was subsequently treated with pyrrolidine and allyl iodide 137 to give an E/Z mixture of the ammonium salts 138. Heating to 80 °C induced the Claisen rearrangement. The newly formed iminium ions 139 underwent intramolecular Mannich cycUzations. The final amine eUmination delivered the spiro ketones 140 with 38% yield as a 2 1 mixture of diastereomers. The formed material should serve as a key compound in diverse cyclopentenone prostaglandine total syntheses (Scheme 10.30). 

The primary cycloadduct 2 eliminates N2 in a retro-DiELS-AiDER reaction and thus affords the 3,4-dihydropyridine 3, which aromatizes to the pyridine derivative 4 by elimination of amine or alcohol. Remarkably, if in the enamine component an N-allyl group is present, the cycloreversion 2 -> 3 is followed - instead of amine elimination - by an intramolecular (4 + 2)-cycloaddition of the N-allyl-C=C-bond to the 2-azadiene unit in 3, which gives rise to formation of N-containing polycycles in high yields [322]. 

One of the advantages of the enamine alkylation reaction over direct alkylation of the ketone under the influenee of strong base is that the major product is the monoalkylated derivative 29,32). When dialkylation is observed, it occurs at the least substituted carbon in contrast to alkylation with base, where the a-disubstituted product is formed. Dialkylation becomes the predominant reaction when a strong organic base is added and an excess of alkyl halide is used (29). Thus 1-N-pyrrolidino-l-cyclo-hexene (28) on treatment with two moles of allyl bromide in the presence of ethyl dicyclohexylamine (a strong organic base which is not alkylated under the reaction conditions) gave a 95 % yield of 2,6-diallylcyclohexanone (29). 

Alkylation of enamines may lead to the formation of N-alkylated product, which on heating is converted to C-alkyl compound (This rearrangement is common with allylic halide, alkyl halide or a-haloacetic ester. 

The overall reaction is best viewed as intramolecular oxidative addition of the C(l)—H bond to the Rh(I) center, causing cyclometalation (25), followed by reductive elimination of an enamine from the Rh(III) intermediate accompanied by allylic transposition. Notably, the allylamine ligand in the initial Rh(I) complex as well as the Rh(III) intermediate has an s-trans conformation with respect to the N—C(l) and C(2)—C(3) bonds, allowing the overall suprafacial 1,3-hydrogen shift to produce the is-configured enamine product. 

Asymmetric allylation.n The chiral enamine 1, derived from the allyl ester of (S)-proline, when treated with this Pd(0) complex at 25° in various solvents provides (S)-( — )-2-allylcyclohexanone (2) in 80-100% ee, the highest enantio-selectivity being observed in CHC13. 

Only allyl and benzyl halides give good yields of C-alkylated aldehydes unless hindered enamines are used64. Otherwise N-alkylation or aldocondensation are often the only reactions observed54a,54ft 6 5. Hindered aldehyde enamines may also be prepared... 

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