Allyhc amines

Morpholine also gives the allyhc amine in high yield. The reaction is thought to involve a known hydridopaUadium-catalyzed isomerization of alkynes to aUenes followed by reaction of the latter with the hydridopalladium complex to give 1-phenyl-substituted q -allylpalladium complexes. These complexes react with amines affording the allylic amines. Primary amines give the diallylic amines. An intramolecular version has been developed for the synthesis of 2-(2-phenyl)-pyrroUdines and -piperidines [319]. 

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. 

Tab. 10.6 summarizes the application of this transformation to a variety of racemic secondary allylic carbonates using the lithium anion of 4-methoxy-N-(p-toluidine)-benzene sulfonamide. The excellent regioselectivity obtained for this type of substitution provided an important advance in the synthesis of N-(arylsulfonyl)anihnes using the metal-catalyzed allyhc amination reaction. The allyhc alcohol derivatives examined... 

While reaction of the acetate 40 as well as the acetyl- and phthalimide derivatives of chiral amine (41b and 41c) proceeded with erythro diastereoselectivity (in accordance with the classical cis effect, minimization of 1,3-allyhc strain) (Table 6, entries 8, 10, 11), for the allylic alcohols 39, primary allyhc amine 41a, silyl enol ethers 42 and enol ether 43 threo selectivity was observed (Table 6, entries 1-7, 9, 12-14) (see also Scheme 24). For allyhc alcohols with an alkyl group R cis to the substituent carrying the hydroxyl group, diastereoselectivity was high (Table 6, entries 1-7) in contrast, stereoselection was low for allylic alcohols which lack such an R cis) substituent (substrates 39h and 39i, see Figure 4). 

An asymmetric variant of this kind of allylic amination, based on their phenylcyclohexanol-derived chiral N-sulfinyl carbamates, was developed by Whitesell et al. (see also Sect. 3.2) (Scheme 34) [85]. After the asymmetric ene reaction with Z-configured olefins (not shown) had occurred, nearly di-astereomerically pure sulfinamides 127 were obtained which were found to be prone to epimerization. Their rapid conversion via O silylation and [2,3]-a rearrangement dehvered the carbamoylated allyhc amines 128 with around 7 1 diastereoselectivity as crystalline compounds that can be recrystallized to enhance their isomeric purity to 95 5. Obviously the imiform absolute configuration at Cl in the ene products 127 was difficult to transfer completely due to the already mentioned ease of epimerization. Unhke the sulfonamides of Delerit (Scheme 33) [84], the carbonyl moiety can easily be cleaved by base treatment. 

North and co-workers required a convenient, catalytic asymmetric synthesis of specifically the (S) -enantiomer of allyHc amines [32]. They prepared a new catalyst, 17, by modifying Tomioka s tridentate amino ether la [19a], but utiHzing only readily available (S)-amino acids. Catalyst 17 was prepared in 45% yield overall from commercially available (S)-proline according to a procedure very similar to that described for the preparation of la (Scheme 10). 

The isomerisation of allyhc amines into the corresponding enamines is an excellent example of asymmetric catalysis, which has been exploited on a commercial basis. The isomerisation of the aUylamine (12.01) with a rhodium/BINAP complex occurs with excellent yield and enantioselectivity to give the enamine (12.02) as the initial product. ... 

In a cascade reaction, Wang and coworkers showed that Pd(0) in the presence of PPh3 could be used to access 1,2,5-substituted pyrroles at modest temperatures in short reaction times (Scheme 15.100). First, allyHc amination via a Pd-catalyzed... 

Pyne et al. were the first to use RCM in the synthesis of a tetrahydropyrrolizidine, namely, 1-epi-australine 93. Ring opening of epoxide 97, readily obtained from 3-butynol, with an enantiopure allyhc amine provided the desired diallylamine in moderate selectivity (Scheme 2.23). Conversion of the diallylamine into oxazolidi-none 98 opened the door to the first RCM cyclization. Portionwise addition of [Ru]-I catalyst (30mol% in total) gave product 95 in 97% yield. When less catalyst was used, significantly lower yields of 95 were obtained. syn-Dihydroxylation of the 3-pyrroHne 95 and an additional five more steps were required to obtain (+)-l-epi-australine (93) as a colorless oil. 

En route to the natural products ent-CP-999,994 (165) and ent-L-733,060 (166), in 2005 Nakano et al. reported a highly enantioselective palladium-catalyzed asymmetric allylic amination (>99% ee) of the allylic acetate 162 using the Ugand L6 [61]. Conversion of the resulting allyhc amine 163 with 3-butenoic acid in the presence of DCC followed by RCM (catalyst [Ru]-II, CH2CI2, reflux, 94%) yielded the piperidinone core structure 164, which was readily converted into the target molecules 165 and 166 (Scheme 2.37). 

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