Allylic amination diastereoselectivity

SCHEME 36. Diastereoselectivity in the reaction of O2 with allylic amines... 

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-allylic strain) (Table 6, entries 8, 10, 11), for the allylic alcohols 39, primary allylic 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 allylic alcohols with an alkyl group R4 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 R4 (cis) substituent (substrates 39h and 39i, see Figure 4). 

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. 

Intramolecular hydroamination of cyclohexa-2,5-dienes has afforded the corresponding bicyclic allylic amines with high selectivity (Scheme 13).80 The reaction does not proceed through a direct hydroamination of one of the diastereotopic alkenes but more likely involves a diastereoselective protonation of a pentadienyl anion, followed by addition of a lithium amide across the double bond of the resulting 1,3-diene and a highly regioselective protonation of the final allylic anion. 

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... 

Unusual -branched Baylis-Hillman adducts have been prepared by Li and coworkers by a novel Et2AlCl promoted domino Michael-aldol reaction of propynoates 50 with organo-cuprates and chiral p-toluenesulfinimines 52 (Scheme 10) [42], These condensations proceeded with very good diastereoselectivity to give allylic amines 53. The selectivity can be explained through the chairlike transition state 54. The anion intermediate approaches the sulfinimine from the sterically less hindered side of the lone pair of electrons. The nucleo-... 

Heathcook et al. have performed a diastereoselective aza-ene reaction using chiral di-(+)-menthyl diazenedicarboxylate 91 as the nitrogen source [54]. Compound 91 was found to react with various alkenes in the presence of 2 equiv. SnCl4, and the corresponding allylic aminated product was obtained in good yield and with de up to 42 %. The problem with this approach was the removal of the chiral menthyl ester auxiliary, which was found to be rather difficult. 

The hydroboration of allylic amine or alcohol derivatives can be used for the preparation of alkylzinc reagents with excellent diastereoselectivity (Equation (34)). Rhodium-catalyzed hydroborations are also compatible... 

On the other hand, hydrozirconation-transmetalation to zinc, when carried out in THF, can be used to prepare allylic amines. When carried out in CH2CI2, however, a different reaction pathway is followed (Scheme 24). Even more, with a different order of introduction of the reagents, it is possible to obtain diastereoselectively homoaUyhc amines instead of the expected aminocyclopropanes. ... 

Tabic 9. Diastereoselectivities in the Epoxidation of Amides of Allylic Amines... 

Diastereoselective [2,3]Sigmatropic Rearrangement Producing Optically Active Allylic Amines... 

Uemura and co-workers have succeeded in diastereoselective imidation of optically active allylic ferrocenyl selenides to give the corresponding optically active allylic amines [40]. Thus, the treatment of optically active cinnamyl ferrocenyl selenides with TsN = IPh or TsNClNa in dichloromethane at 0°C afforded the allylic amines in moderate yields with high enantiomeric excesses (Scheme 26). 

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. 

The Petasis reaction is a mild multicomponent reaction that allows the conden sation of a boronic acid, an amine, and a carbonyl derivative to generate an allylic amine. Although several diastereoselective Petasis reactions have been reported [106], the first catalytic asymmetric reaction was described in 2008 (Scheme 1.29) [107]. It was shown that the condensation proceeds in high yields and enantiomeric excesses, affording the corresponding protected a vinylglycine derivatives. 

Iodomethyl)oxazolidinones in high yields (>90%) with moderate to high diastereoselectivities from allylic amines. ... 

Example 3, Diastereoselective Simmons-Smith cyclopropanations of allylic amines and carbamates ... 

Allylic systems frequently represent very popular substrates for the synthesis of epoxides. For example, hydrogen bonding proved influential during diastereoselective epoxidation of a series of cyclic and acyclic allylic amines... 

Scheme 15.43 Switch in diastereoselectivity for pallaciinm catalyzed allylic amination/r 2.31-rearrangement. 

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