Sharpless catalytic asymmetric aminohydroxylation

Sharpless catalytic asymmetric aminohydroxylation (AA) provides a direct and efficient route to the taxol side chain as well as a number of other natural products and synthetic ligands. The required asymmetry of the taxol side chain was controlled by (DHQ)2-PHAL, and hydroxyla-tion was achieved with potassium osmate (K20s02(0H)4). Various N-haloamide salts were investigated, and yields and percentage ee were good to excellent under different conditions. For example, reaction of methyl cinnamate under Sharpless catalytic AA conditions gave (2R,3S) N-tosyl-3-phenyl isoserine 7.3.1 in 82% ee in 69% yield. Compound 7.3.1 was then converted to the taxol side chain acid in two steps in good yield (262). 

In 1975 Sharpless and coworkers discovered the stoichiometric aminohydrox-ylation of alkenes by alkylimido osmium compounds leading to protected vicinal aminoalcohols [1,2]. Shortly after, an improved procedure was reported employing catalytic amounts of osmium tetroxide and a nitrogen source (N-chlo-ro-N-metallosulfonamides or carbamates) to generate the active imido osmium species in situ [3-8]. Stoichiometric enantioselective aminohydroxylations were first reported in 1994 [9]. Finally, in 1996 the first report on a catalytic asymmetric aminohydroxylation (AA) was published [10]. During recent years, several reviews have covered the AA reaction [11-16]. 

Sharpless and co-workers first reported the aminohydroxyIation of alkenes in 1975 and have subsequently extended the reaction into an efficient one-step catalytic asymmetric aminohydroxylation. This reaction uses an osmium catalyst [K20s02(OH)4], chloramine salt (such as chloramine T see Chapter 7, section 7.6) as the oxidant and cinchona alkaloid 1.71 or 1.72 as the chiral ligand. For example, asymmetric aminohydroxylation of styrene (1.73) could produce two regioisomeric amino alcohols 1.74 and 1.75. Using Sharpless asymmetric aminohydroxylation, (IR)-N-ethoxycarbonyl-l-phenyl-2-hydroxyethylamine (1.74) was obtained by O Brien et al as the major product and with high enantiomeric excess than its regioisomeric counterpart (R)-N-ethoxycarbonyl-2-phenyl-2-hydroxyethylamine (1.75). The corresponding free amino alcohols were obtained by deprotection of ethyl carbamate (urethane) derivatives. 

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. 

Bruncko, M., Schlingloff, G., Sharpless, K. B. N-Bromoacetamide - a new nitrogen source for the catalytic asymmetric aminohydroxylation of olefins. Angew. Chem., Int. Ed. Engl. 1997, 36, 1483-1486. 

Demko, Z. P., Bartsch, M., Sharpless, K. B. Primary Amides. A General Nitrogen Source for Catalytic Asymmetric Aminohydroxylation of Olefins. Org. Lett. 2000, 2, 2221-2223. 

Catalytic asymmetric aminohydroxylation using Os(VIII) and Sharpless cinchona alkaloid ligand has been applied to a,p- and P,Y-unsaturated phosphonate substrates (Scheme 48). The reaction only works for the aryl substituted examples (287) and although initial e.e. s are sometimes low, they can be increased to >90% by a single recrystallisation. The phosphonic acid analogue... 

The anticancer drugs Taxol and Taxotere feature a (2R, 35)-V-benzoyl phenylisoserine as side chain. A number of stereoselective syntheses of this moiety have been reported. Among them, the preparation based on the catalytic asymmetric aminohydroxylation protocol recently developed by Sharpless and reported in Fig. 26 seems particularly attractive [77]. 

Subsequently, stoichiometric asymmetric aminohydroxylation was reported. Recently, it was found by Sharpless that through the combination of chloramine-T/Os04 catalyst with phthalazine ligands used in the asymmetric dihydroxylation reaction, catalytic asymmetric aminohydroxylation of olefins was realized in aqueous acetonitrile or tert-butanol (Scheme 3.3). The use of aqueous tert-butanol is advantageous when the reaction product is not soluble. In this case, essentially pure products can be isolated by a simple filtration and the toluenesulfonamide byproduct remains in the mother liquor. A variety of olefins can be aminohydroxylated in this way (Table 3.1). The reaction is not only performed in aqueous medium but it is also not sensitive to oxygen. Electron-deficient olefins such as fumarate reacted similarly with high ee values. 

Li G, Sharpless KB (1996) Catalytic Asymmetric Aminohydroxylation Provides a Short Taxol Side-chain Synthesis. Acta Chem Scand 50 649... 

Sharpless has noted that the regiochemical outcome with cinnamyl esters is coupled to the ligand system employed [237]. Thus, when AQN ligands (314), were used, benzylic alcohols were preferentially obtained, rather than the benzylic amines observed with PHAL ligands (311). This selectivity trend was utilized by Joullie in the synthesis of the potent microtubule assembly inhibitor ustiloxin D (356, Scheme 9.45) [238]. Under optimized conditions, cinnamyl ester 354 was converted selectively into the desired benzylic alcohol 355 (58% yield). This constitutes one of the structurally more complex substrates to have successfully been employed in catalytic asymmetric aminohydroxylation [238, 239]. 

Thomas AA, Sharpless KB (1999) The Catalytic asymmetric aminohydroxylation of unsaturated phosphonates. J Org Chem 64 8379-8385... 

In 2001, K. B. Sharpless won the Nobel Prize in Chemistry for his work on asymmetric aminohydroxylation and asymmetric epoxidation °. These stereoselective oxidation reactions are powerful catalytic asymmetric methods that have revolutionized synthetic organic chemistry. 

Aminohydroxylation of unsymmetrically substituted alkenes, in contrast to dihydroxylation, may give two possible regioisomers of aminoalcohol derivatives but asymmetric aminohydroxylation, by using the same catalytic system as that used for Sharpless asymmetric dihydroxylation, can be highly regioselective as well as enantioselective. 

The aziridino alcohols that have been prepared and tested as chiral promoters for the catalytic asymmetric dialkylzinc alkylation of imines are shown in Fig. 4. The authors have investigated three different approaches to obtain the ligands in enantiomerically pure form (1) the use of the chiral pool, (2) the Sharpless asymmetric aminohydroxylation, and (3) the Sharpless asymmetric dihydroxylation. The starting materials for the preparation of the aziridino alcohols 30, 31a-h, 32a,b, and 33 were the readily available amino acids L-serine, L-threonine, and aZZo-L-threonine. 

Aminohydroxylation of Alkenes. Sharpless asymmetric aminohydroxylation (AA) allows for the catalytic and enantios-elective symthesis of protected vicinal aminoalcohols in a single step. This reaction is significant as it applies to the synthesis of a wide variety of biologically active agents and natural products. For example, new monoterpene /3-amino alcohols can effectively be synthesized from (+)-2-carene, (+)-3-carene, (—)-/3-pinene, and... 

In 1975, Sharpless et al. reported that imino-osmium trioxides underwent aminohydroxylation (Scheme 54).208,209 t0 perform aminohydroxylation with high efficiency, regio-, chemo-, and enantioselectivity must be addressed. This had made the practical realization of aminohydroxylation difficult. However, the development of asymmetric dihydroxylation, as described in the preceding section, propelled the study of asymmetric aminohydroxylatyion forward and, in 1996, Sharpless et al. reported a highly enantioselective version of catalytic aminohydroxylation... 

Since the discovery of the catalytic AD in 1987, there have been numerous attempts in the Sharpless group to render the old catalytic aminohydroxylation process asymmetric [7]. Until recently, the obvious approach of adding the AD s chiral ligands, but otherwise staying close to the original protocol [3] led to extremly slow catalyst turnover. The initial breakthrough [8] was not due to a sudden con-... 

G.4 Amino-Hydroxylation. A related reaction to asymmetric dihydroxylation is the asymmetric amino-hydroxylation of olefins, forming vic-aminoalcohols. The v/c-hydroxyamino group is found in many biologically important molecules, such as the P-amino acid 3.10 (the side-chain of taxol). In the mid-1970s, Sharpless reported that the trihydrate of N-chloro-p-toluenesulfonamide sodium salt (chloramine-T) reacts with olefins in the presence of a catalytic amount of osmium tetroxide to produce vicinal hydroxyl p-toluenesulfonamides (Eq. 3.16). Aminohydroxylation was also promoted by palladium. ... 

Contrary to the osmium-catalyzed dihydroxylation (DH) [80], the aminohydroxylation (AH) [18, 81] adds two different heteroatoms (N, O) to double bonds. It provides straightforward access to the amino alcohol fragment present in a broad variety of namral products (Fig. 8). Numerous reviews [20, 22, 82-87] have been published, among others, by its inventor K. B. Sharpless [17, 20, 88], who also rendered it asymmetric and catalytic at the same time in 1996 [89,90],... 

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