Allyl amines reduction

The formation of an enamine from an a,a-disubstituted cyclopentanone and its reaction with methyl acrylate was used in a synthesis of clovene (JOS). In a synthetic route to aspidospermine, a cyclic enamine reacted with methyl acrylate to form an imonium salt, which regenerated a new cyclic enamine and allowed a subsequent internal enamine acylation reaction (309,310). The required cyclic enamine could not be obtained in this instance by base isomerization of the allylic amine precursor, but was obtained by mercuric acetate oxidation of its reduction product. Condensation of a dihydronaphthalene carboxylic ester with an enamine has also been reported (311). 

The first of the nudeophilic ring-opening reactions of vinylaziridines discussed in this section is diborane reduction, developed by Laurent and coworkers in 1976 (Scheme 2.24). Treatment of N-unsubstituted vinylaziridines 89 with B2H6 gives allyl amines 92 by SN2 reduction via cyclic intermediates 90 [40]. In contrast, treatment with 9-BBN gives 2-(hydroxyethyl)aziridines 93 after oxidative workup (Scheme 2.25) [41]. 

The reductive coupling of of dienes containing amine groups in the backbones allows for the production of alkaloid skeletons in relatively few steps [36,46,47]. Epilupinine 80 was formed in 51% yield after oxidation by treatment of the tertiary amine 81 with PhMeSiEh in the presence of catalytic 70 [46]. Notably, none of the trans isomer was observed in the product mixture (Eq. 11). The Cp fuMcTIIF was found to catalyze cyclization of unsubstituted allyl amine 82 to provide 83. This reaction proceeded in shorter time and with increased yield relative to the same reaction with 70 (Eq. 12) [47]. Substitution of either alkene prevented cyclization, possibly due to competitive intramolecular stabilization of the metal by nitrogen preventing coordination of the substituted olefin, and resulted in hydrosilylation of the less substituted olefin. 

O-Methanesulphonyloximes of a,/i-unsaturated ketones yield allylic amines on reduction with lithium aluminium hydride (equation 78)207. 

In this case an active dendritic Pd°-species could be generated by hydrazine reduction and subsequently used in a DMF/heptane mixture at 75 °C for the stereoselective allylic amination. After completion of the reaction and cooling to room temperature, the catalysts can be recovered by simple phase separation. 

Additionally, 1,2-dihydroxyethylene dipeptide analogues without the C-terminal carboxylic acid have been used to obtain aspartyl proteases inhibitors.[641 These efforts include stereoselective alkylation of imines, one-pot reductive amination of epoxy ketones, ring opening of epoxides with sodium azide, diastereoselective dihydroxylation of allylic amines, and enzymatic resolution and stereocontrolled intramolecular amidation. 

Primary ally lie amines1 In the presence of this catalyst, allylic chlorides or acetates react with sodium p-toluenesulfonamide in THF/DMSO (80 20) to form the corresponding allylic sulfonamide in 60-85% yield. The products are converted into primary allylic amines on reductive cleavage (sodium naphthalenide). 

Ally lie amines.1 The trimethylsilylisoxazolidines formed on cycloaddition of vinyltrimethylsilanes with nitrones (12, 566) are converted on reductive cleavage of the N—O bond and concomitant Peterson elimination of (CH3)3SiOH into allylic amines. 

Ab Initio MO calculations of a model complex Rh(PH3)2(NH3)(CH2=CHCH2NH2) were earned out to shed light to the detailed mechanism of Rh(l)-catalyzed isomerization of allylic amines to enamines.5 This study suggests that the square-planar [RhiPHjyNHjXCf CHCHjNHj) complex is transformed to [Rh(PH3)2(NH3)(( )-CH3CH=CHNH2)]+ via intramolecular oxidative addition of the C(l)-H bond to the Rh(I) center, giving a distorted-octahedral Rh(lll) hydride intermediate, followed by reductive elimination accompanied by allylic transposition. 

Optically active sulfonimidamides react with benzylic and allylic methylene groups to give the formal product of nitrene CH insertion.75 The reaction is catalysed by dirhodium complexes and delivers rather mixed results, both de and yield being (g) substrate dependent. The authors finish the transformation by removing the sulfonim-idamide by reduction to leave a benzylic or allylic amine. 

A desymmetrization of cyclohexa-2,5-dienes (22) and (24), obtained by Birch reductive alkylation, through a diastereoselective intramolecular hydroamination led with high selectivity to the corresponding bicyclic allylic amines (23) and (25) (Scheme 6).19... 

A more concise route to ( )-cherylline was also devised and commenced with the reductive animation of isovanillin with methylamine followed by reaction of the intermediate benzylamine with vinyl triphenylphosphonium bromide to provide the aminophosphonium salt 619. Sequential treatment of 619 with n-butyllithium and the quinone ketal 615 followed by reaction of the resulting crude allylic amine 620 with boron trifluoride etherate gave the phenolic amine 618 in good overall yield (225). 

Other types of allylic amination reactions include a variety of indirect approaches such as reduction of a,P-unsaturated imines and oximes, rearrangement of aziridines, and elimination of water from vicinal amino alcohols. However, these reactions will not be considered in this chapter [2]. 

Scheme 9 that both the molybdenum and iron complexes can catalyze the allylic amination of nonfunctionalized alkenes with an ene-like transposition of the double bond, but also that the yield of the allyl amine formed, 113, is moderate to high. It is generally found that higher substituted alkenes tend to give the best yields, and un-symmetrical alkenes (trisubstituted) react with virtually complete regioselectivity, as only one isomer is detected. The byproducts are primarily azoxybenzene and aniline, which arise from condensation of nitrosobenzene with phenyl hydroxylamine and reduction of phenyl hydroxylamine, respectively. 

The use of nitro arenes as the nitrogen fragment donor in combination with CO under catalytic, and reductive, conditions has also been presented by Nicholas et al. who have found that [CpFe(CO)2]2 can be used as the catalyst [69]. A variety of different alkenes were tested, and a-methyl styrene gave the highest yield of the allyl amine 113 when nitrobenzene was used. The yield of the allyl amine depends markedly on the structure of both the alkene and the nitro compounds. 

Further functionality (i.e., 4-oxo) has been introduced by the cyclization of a-allyloxy-carbonylnitrones, which have traditionally been problematic to obtain. Tamura and co-workers have reported that simple alkoxycarbonylnitrones (e.g., (243)) undergo transesterification and cyclization with various allylic alcohols in the presence of titanium isopropoxide (Scheme 43) <95T107, 95T119). Alternatively, allyl a-oximinocarboxylates (246) are converted in situ to nitrones (247) and further cyclized to the bicyclic heterocycles (248) (Scheme 44) <91T4495>. Tetrahydro-1 //-pyrrolo[3,4-c]isoxazoles (250) have been prepared by the condensation of C-acylnitrones with allyl amines <78AJC2013> further reduction of the bicycles (250) with sodium borohydride affords the 3-oxa-2,7-diazabicyclo[3.3.0]octane (251) (Scheme 45). 

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). 

These amines can be deprotected under reduction conditions (Pd-C/R0H/HC02NH4 or Na/NH3). The allyl amines can be deprotected by oxidative cleavage with ozone (dimethyl-sulfide work up) or with KMn04 in acetone. 

N-Allylation of aziridines is often complicated by side reactions. The classical solution to this problem, reductive amination, can also be problematic due to the increased strain energy of the aziridinium intermediate. A way to avoid this difficulty was developed by Yudin and co-workers <2005JA17516, 2004JA5086>. The results obtained showed that NH-aziridines such as 197 or 198 underwent a palladium-catalyzed allylic amination with various allyl acetates affording the desired allylated product 199 and 200 with high levels of regioselectivity and in high isolated yields (Scheme 54). 

Chiral tertiary allylic amines 191 with /ra r-2-phenylsulfonyl-3-phenyloxaziridine 33 also gave rise to amine A -oxides 192, which underwent the [2,3]-Meisenheimer rearrangement to hydroxylamines 193 with a high level of stereoselectivity (Table 14) <1999J(P1)2327>. Reduction of 193 gave the corresponding allylic alcohols 194. 

Reduction of nitroarenes with CO in the presence of alkenes with allylic hydrogen gives allyl amines (Eq. 11.55) [104]. 

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