Aminohydroxylation diastereoselective

The first examples of the diastereoselective aminohydroxylation of chiral acryl amides, R3CH=C(R2)CONHCH (Me)R1, have been reported. The reaction is believed to proceed within the so-called second catalytic cycle with diastereoisomeric excesses (g) reaching >99 1. The reaction relies solely on the stereochemical information provided by the enantiomerically pure starting materials. A stereochemical model for the observed asymmetric induction has been proposed.128... 

Another substrate class, for which the outcomes of a radical and a carbocationic process are opposite, are indoles (Fig. 85) [418], Indeed, when oxaziridines 315a or 315c were treated with indoles 314c in the presence of 2 or 10 mol% of C11CI2/ TBAC oxazolidinoindolines 316c were obtained as the exclusive products in 53-90% yield. The reaction is applicable to 2-, 3-, and 2,3-disubstituted indoles. Chiral indole derivatives acylated with (S)-proline units at nitrogen underwent asymmetric diastereoselective aminohydroxylation reactions with 86-91% de. Tricyclic hemiaminals derived from tryptamine derivatives could be transformed to pyrrolidinoindolines, which are core structures of a number of alkaloids. 

The aminohydroxylation of racemic Baylis-Hillman alkenes provided regio-isomerically pure, racemic mixtures of the a - hydroxy- (3 - am i no esters, with the syn (diol) product as the major diastereomer (Table 11) [97]. The diastereoselectivity increased with increasing size of either the allylic substituent or the ester group. As observed in other studies of related substrates [53,103-105], neither the rate, the selectivity, nor the yield were noticeably affected when a chiral ligand (e.g., (DHQ)2PHAL) was added and enantioselective aminohydroxylation could not be obtained. 

Table 11 Diastereoselective aminohydroxylation of Baylis-Hillman alkenes...

The Sharpless regioreversed asymmetric aminohydroxylation protocol was used as a key step in the total synthesis of ustiloxin D by M.M. Joullie and co-workers.The ( )-ethyl cinnamate derivative was subjected to in situ generated sodium salt of the N-Cbz chloroamine in the presence of catalytic amounts of the anthraquinone-based chiral ligand to afford the desired A/-Cbz protected (2S,3R)-(3-hydroxy amino ester in good yield and with good diastereoselectivity. 

The mnemonic device used to predict the sense of enantioselectivity in the AD reaction can also be used in the AA process. Typical examples include the asymmetric aminohydroxylation of alkenes (5.63-5.67), all with excellent enantioselectivity. Heterocyclic groups are tolerated in the AA reaction and high ees have been obtained for the aminohydroxylation of furanoyl acrylates such as (5.65). ° In common with the AD reaction, pyrrolyl- and pyridyl-substituted olefins are difficult substrates and blocking of the nitrogen is required for enantioselective aminohydroxylation. However, indoles such as (5.66) undergo aminohydroxylation with good ee. The AA reaction has also been applied to the desymmetrisation of dienylsilane (5.67) by Landais and coworkers. Whilst the enantioselectivity is not perfect, the reaction is still remarkably regio- and diastereoselective. 

A ligand-independent, osmium-catalyzed aminohydroxylation of MBH adduct has been developed by Sharpless et al. (Scheme 3.202). The yield, rate and selectivity of this reaction are not affected by the addition of cinchona alkaloid ligands. The diastereoselectivity for the aminohydroxylation is influenced by the aldehyde-derived substituent, while the acrylate-derived substituent has a minimal effect. Various derivatives and close analogs of the MBH product-core failed to aminohydroxylate, emphasizing the unique reactivity of this class of olefins. 

The metal-free intramolecular 5 Nf-exo-trig aminohydroxylation of Al-alkenyl-sulfonamides (81) can be effected by oxone activated with Brpnsted acid as catalyst. The reaction thus proceeds via (83) and affords the prolinol derivatives (82). Although the scheme suggests that the reaction should be diastereoselective, this issue has not been addressed and there is also an incorrect use of curly arrows in this paper. 

Olefins have a rich history in organic chemistry and consequently there is a vast array of transformations available to this fundamental functional group. This chapter discusses the classic methods for stereoselective oxidations of olefins, spanning the range from diastereoselective [16-18] and enantioselec-tive [19-29] formation of epoxides to their asymmetric ring-opening reactions [30-33], stereoselective formation of aziridines [34—37], iodolactoniza-tions and other olefin cyclizations induced by electrophiles [38, 39], dihy-droxylations [40-49], and aminohydroxylations [47, 50] (Figure 9.1). 

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