N-allyl amines

The N-protected allylic amines as phosphorated N-allylic amines also hinder N-B coordination, and clean hydroboration is achieved by 9-BBN [37] (Chart 5.6). 

Duchene and Parrain developed a one-pot allylic amina-tion/palladium-catalyzed Sonogashira cross-coupling and heterocyclization process for the preparation of 1,2,4-trisub-stituted and 1,3-disubstituted pyrroles starting from diiodo-butenoic acid, a primary amine, and a terminal alkyne [49], Scheme 3.27 shows a plausible mechanism for this transformation. The initial C—N allylic amination, followed by a Sonogashira cross-coupling and an intramolecular hydroam-ination, affords a dihydroexoalkylidene pyrrole XIX, which rearranges into pyrrole 39. The reaction is influenced by the... 

Addition to C=N Allylic amination Amides from aldehydes Amides from nitriles Aminals from aldehydes Amination of aryl halides a - Aminoallylation Aminocarbonylation Aminohydroxylation Arylation... 

Selenium diimides react in a manner similar to SeOa with unsaturated organic compounds. The first report of BuN=Sc=N Bu described its use as an in situ reagent for allylic amination of olefins and acetylenes. Improved procedures for this process (Eq. 10.5) and for the diamination of 1,3-dienes (Eq. 10.6) have been developed using the reagents RN=Se=NR [R = para-toluenesulfonyl (Ts), ort/io-nitrobenzenesulfonyl (Ns)]. ... 

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]. 

Electron transfer to vinylaziridines results in ring-opening reactions, yielding allyl amines. Treatment of 268 with SmI2/DMEA (N,N-dimethylethanolamine) provided allyl amine 269 as a 2 1 mixture of olefmic isomers in 88% yield (Scheme 2.66) [97]. 

Overman LE, Owen CE, Pavan MM, Richards CJ (2003) Catalytic asymmetric rearrangement of allylic N-aryl trifluoroacetimidates. A useful method for transforming prochiral allylic alcohols to chiral allylic amines. Org Lett 5 1809-1812... 

Fischer DF, Xin ZQ, Peters R (2007) Asymmetric formation of allylic amines with N-substimted quaternary stereocenters by Pd -catalyzed Aza-Claisen rearrangements. Angew Chem Int Ed 46 7704-7707... 

Enantioselectivity (which is hnked to the regioselectivity of the attack of the nucleophile to the coordinated allyl) in the allylic amination of 1,3-diphenyl-allyl ethyl carbonate was also very low compared to the P-N system. This was attributed to the comparable fran -influence of P and NHC functionalities, leading to poor regioselec-tion of the two aUyl termini trans to the P and NHC ligands by the nucleophile [95],... 

Scheme 4.17 Generation of secondary amine 33 by deprotection of N-allyl group enables access to functionalized core structures...

Basset and co-workers (91) found that amino olefins such as allyl amine and the /V.N-dimethyl derivative failed to undergo metathesis, but that unsaturated quaternary ammonium salts were active at 25°C with zero-valent tungsten and molybdenum catalysts when activated with molecular oxygen. Molar ratios of olefin/(mesitylene)W(CO)3/C2H5AlCl2/02 and olefin/Mo(NO)2Cl2[P(Ph)3]/C2H5AlCl2 were 20/1/24/80 and 20/1/24, respectively. Yields were in the 8-23% range. 

Allylic amination is important for the solid-phase organic synthesis.15 The solid-phase allylic aminations are devised into the G-N bond formation on solid support and the deprotection of allyl ethers. As a novel deprotection method, the palladium-catalyzed cyclization-cleavage strategy was reported by Brown et al. (Equation (4)).15a,15b The solid-phase synthesis of several pyrrolidines 70 was achieved by using palladium-catalyzed nucleophilic cleavage of allylic linkages of 69. 

Isomerization of allylic amines is another example of the application of the BINAP complex. Rh BINAP complex catalyzes the isomerization of N,N-diethylnerylamine 40 generated from myrcene 39 with 76-96% optical yield. Compound (R)-citronellal (R)-42. prepared through hydrolysis of (R)-41, is then cyclized by zinc bromide treatment.49 Catalytic hydrogenation then completes the synthesis of (—)-menthol. This enantioselective catalysis allows the annual production of about 1500 tons of menthol and other terpenic substances by Takasago International Corporation.50... 

Radical cyclization of N-alkenylamino acid derivatives Proline derivatives can be obtained by cyclization of N-alkenyl amino acid derivatives. Thus the (3-iodo allylic amine 2, prepared in 54% yield from threonine, cyclizes in the presence... 

Scheme 7. Preparation of benzo-fused six-membered heterocycles 26-30 and 33 from 2-halophenyl 2-bromobenzyl ethers, amines, and thioether 25 and 32. i) fBuLi (3.5 equiv for 25a, b, 3.3 equiv for 25c,d, and 32), THF, -110 20°C ii)E+, -78 20°C iii) for X = N(allyl), DIBAL-H (1.5 equiv), cat. [NiCl2(dppp)], toluene, 20 °C.

Grafting can also provide the monolithic polymers with rather unexpected properties. For example, the two-step grafting procedure summarized in Fig. 7, which involves the vinylization of the pore surface by reaction of the epoxide moiety with allyl amine, and a subsequent in situ radical polymerization of N-isopropylacrylamide (NIPAAm) initiated by azobisisobutyronitrile within these pores leads to a composite that changes its properties in response to external temperature [76]. 

Secondary allylic amines 184 have been prepared from aldehydes 181 (R1 = H, Me or Ph R2 = Me, Et or H) by the following sequence treatment with an amine R3NH2 (R3 = i-Pr, t-Bu, cyclohexyl or PhCH2) yields an imine 182, which is chlorinated by N-chlorosuccinimide. Dehydrochlorination of the resulting chloro compound with potassium t-butoxide gives an allylic imine 183, which is reduced to the product by means of methanolic sodium borohydride191. 

The silylated tin compound 199, obtained from tributyltin hydride and N-bis(trimethylsilyl)propargylamine (198) in the presence of a trace of AIBN (2,2/-azobisisobutyronitrile), is a versatile reagent for the preparation of allylic amines. Treatment with aryl bromides ArBr (Ar = Ph, 4-MeOCgH4, 4-O2NC6H4 etc.) under Pd(PPh3)4 catalysis yields the silylated amines 200, which are hydrolysed by acids to the free amines 201. 199 is converted into the lithium compound 202, which is transformed into 203 by aqueous ammonium chloride and into 204 by the action of alkyl halides RX (R = Me, Et or allyl) (equation 76)204. 

Scheme 5 Enantioselective iridium-catalyzed hydrogenation of alkynes in the presence of N-arylsulfonyl imines to furnish trisubstituted allylic amines...

Intramolecular allylic aminations (Scheme 9.20) proceeded with low catalytic efficiency and with ee-values <90% if procedure (a) (cf. Section 9.2.3.2) was used-that is, the catalyst was not activated [18]. The effect of catalyst activation [procedure (c)] was pronounced [18, 22a] for example, activation with TBD increased the rate of formation of N-benzyl-2-vinylpiperidine by a factor of about 1000. Also notable was the fact that substrate concentration as high as 1M was possible, thereby demonstrating the high preference of intramolecular over intermolecular substitutions leading to oligomers. 

N-Boc-N-(but-2-enoyl)amine is an excellent pronucleophile for the Ir-catalyzed allylic amination under salt-free conditions (cf. Table 9.3, entries 15-18). The products were subjected to RCM with good results, even upon application of the Grubbs I catalyst (Scheme 9.29) [27bj. The resultant N-Boc protected a,P-unsaturated y-lactams are valuable chiral intermediates with appUcations in natural products synthesis and medicinal chemistry. 

Evans and co-workers demonstrated that rhodium-catalyzed allylic amination of enantiomerically enriched acyclic unsymmetrical allylic carbonates occurs with excellent regio- and enantiospedfidty (Tab. 10.5) [35]. Interestingly, while the classical nitrogen nucleophiles furnished allylic amination products in poor yield and with modest regioselectivity, the lithium anion of N-toluenesulfonyl-N-alkylamines proved optimal, in terms of nucleophilicity and basicity. 

Scheme 10.8 outlines the application of rhodium-catalyzed allyhc amination to the preparation of (il)-homophenylalanine (J )-38, a component of numerous biologically active agents [36]. The enantiospecific rhodium-catalyzed allylic amination of (l )-35 with the lithium anion of N-benzyl-2-nitrobenzenesulfonamide furmshed aUylamine (R)-36 in 87% yield (2° 1° = 55 1 >99% cee) [37]. The N-2-nitrobenzenesulfonamide was employed to facilitate its removal under mild reaction conditions. Hence, oxidative cleavage of the alkene (R)-36 followed by deprotection furnished the amino ester R)-37 [37, 38]. Hydrogenation of the hydrochloride salt of (l )-37 followed by acid-catalyzed hydrolysis of the ester afforded (i )-homophenylalanine (R)-3S in 97% overall yield. 

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