Sharpless AA reaction

An original modification of the Sharpless AA reaction using excess of N-bromoacetamide as nitrogen/bromine source appeared particularly useful method for the transformation of 2-aryl-vinylphosphonates (338) into syn-2-aryl-2-amino-l-bromoethyl phosphonates (339) (Scheme 91). ... 

It is also important to note that the obtained regioselectivity of this aminoacetoxylation reaction is opposite to the one observed in the seminal Sharpless asymmetric aminohydroxylation reaction (Sharpless AA reaction) [120]. Although processes of palladium(IV) catalysis currently cannot induce enantioselectivity, future development should render this unique reactivity complementary to existing enantioselective transformations. 

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]. 

A variation on the Sharpless dihydroxylation methodology allows for the preparation of amino alcohols. This reaction is known as the AA reaction, and it has been... 

The Sharpless asymmetric hydroxylation can take one of two forms, the initially developed asymmetric dihydroxylation (AD)1 or the more recent variation, asymmetric aminohydroxylation (AA).2 In the case of AD, the product is a 1,2-diol, whereas in the AA reaction, a 1,2-amino alcohol is the desired product. These reactions involve the asymmetric transformation of an alkene to a vicinally functionalized alcohol mediated by osmium tetraoxide in the presence of chiral ligands (e.g., (DHQD)2-PHAL or (DHQ)2-PHAL). A mixture of these reagents (ligand, osmium, base, and oxidant) is commercially available and is sold under the name of AD-mix p or AD-mix a (vide infra). 

Finally, Sharpless recendy described the successful use of adenine-based nitrenoids for the AA. Although the yields were good and the regioselectivities were high, the reaction only proceeded in solvent systems containing alcohol-water mixtures and no enantioselecdvity was observed [80]. 

K.B. Sharpless (1941-) studied at Stanford and was first appointed atMIT but is now at the Scripps Institute in California. His undoubted claim to fame rests on the invention of no fewerthan three reactions of immense significance AE (asymmetric epoxidation) and AD (asymmetric dihydroxylation) are discussed in this chapter. The third reaction, AA (asymmetric aminohydroxylation) has still to reach the perfection of the first two. 

In 1996, Sharpless reported that modification of the AD reaction, by the inclusion of a nitrogen source, which also functions as an oxidant, gives an asymmetric aminohydroxylation (AA). > ... 

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... 

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). 

---