N-sulfonyloxy carbamates as reoxidants for the tethered aminohydroxylation reaction

The use of N-sulfonyloxy carbamates as reoxidants for the tethered aminohydroxylation (TA) reaction is reported. These new conditions obviate the requirement for lithium hydroxide and tBuOCl in the oxidation mixture. In addition to providing aminohydroxylation products in good yields, the catalyst loadings can be reduced to just 1 mol % osmium. Moreover, for the first time, homoallylic alcohols are now viable substrates for the TA reaction.     

Synthesis of the dysiherbaine tetrahydropyran core employing a tethered aminohydroxylation reaction

A stereocontrolled and scalable synthesis of an advanced intermediate of the dysiherbaine tetrahydropyran core has been achieved in 11 steps and 27% overall yield. The key feature of this synthetic approach is the application of the Donohoe tethered aminohydroxylation reaction to install the amino diol and establish the four contiguous syn stereocenters on the tetrahydropyran ring.     

Tethered aminohydroxylation using acyclic homo-allylic sulfamate esters and sulfonamides as substrates

Homo-allylic sulfamate esters and sulfonamides are shown to be useful substrates for the tethered aminohydroxylation (TA) reaction. The sulfamate esters undergo the TA reaction delivering 1,2,3-oxathiazinane products whereas the sulfonamides give 1,2-thiazinane products. A range of acyclic homo-allylic sulfamate esters were prepared and subjected to the TA reaction to establish the scope of the process. Nucleophilic ring-opening reactions of the 1,2,3-oxathiazinane products are also described.     

不对称氨羟化反应

介绍了Sharpless等人新近发现的不对称氨羟化反应,该反应可将烯烃直接转化成为手性β-氨基醇类化合物。对于有些烯烃,Sharpless不对称氨羟化反应具有高的区域选择性(20:1)和高的对映选择性(>98%e.e.)。     

Synthesis of the dysiherbaine tetrahydropyran core utilizing improved tethered aminohydroxylation conditions

A concise stereoselective route to the dysiherbaine tetrahydropyran core was achieved in nine steps and 39% overall yield. Donohoe’s improved tethered aminohydroxylation conditions were employed to concurrently install the amino and alcohol groups and construct the tetrahydropyran ring, which features four contiguous cis-stereocenters.     

The preparation of simplified scyphostatin analogues using a tethered aminohydroxylation (TA) strategy

The first tethered aminohydroxylation reaction employing a tertiary alcohol is reported as part of a route to prepare analogues of the naturally occurring sphingomyelinase inhibitor, scyphostatin. The tethered aminohydroxylation of 1-allylcyclohexanol produces the β-amino alcohol product, in protected form, with the required regiochemistry. Two approaches to the installation of the lipophilic side chain are described and the successful route used to prepare five novel scyphostatin analogues, one containing the natural lower side chain.     

The tethered aminohydroxylation (TA) of cyclic allylic carbamates

The tethered aminohydroxylation of cyclic allylic carbamates is described using catalytic amounts of potassium osmate. The mechanism of reaction involves formation of an imido-osmium complex which adds intramolecularly to alkenes with complete control of both regio- and stereoselectivity: the formation of syn-aminodiol motifs is now straightforward using this chemistry. Proof of the mechanism was obtained with an X-ray crystal structure of an azaglycolate osmate ester intermediate.     

Remote acyclic stereocontrol. Chiral synthesis of (+)-pedamide

Synthesis of optically active pedamide (3), one of the tetrahydropyran moieties of the potent insect poison pederine (1), has been accomplished through a new, remote controlled asymmetric reduction of a ketone as key step.     

A short enantioselective synthesis of (−)-chloramphenicol and (+)-thiamphenicol using tethered aminohydroxylation

An efficient enantioselective synthesis of (−)-chloramphenicol (1) and (+)-thiamphenicol (2) is described. These antibiotics have been synthesized from commercially available 4-nitrobenzaldehyde and 4-(methylthio)benzaldehyde, respectively, using tethered aminohydroxylation and Sharpless asymmetric epoxidation as the chirality inducing steps.     

Allylic stereocontrol of the intramolecular Diels-Alder reaction

The stereochemical outcome of the intramolecular Diels-Alder reaction of ester-linked 1,3,8-nonatrienes can be controlled by substituents about a stereogenic center attached to C1. The scope and limitations of this approach have been investigated, with variation in substrate structure about the allylic stereocenter and the dienophile. The stereochemical outcomes of these reactions are explained by reference to B3 LYP/6-31G(d) transition structures. New insights into the conformational preferences of allylic alcohol derivatives are reported, results which allow an explanation of the differing levels of pi-diastereofacial selectivity and cis/trans (i.e. endo/exo) selectivity from the reaction.     

Engineering stereocontrol into an aldolase-catalysed reaction

A novel thermostable aldolase has been developed for synthetic application, and substrate engineering has been used to induce stereocontrol into aldol reactions of this naturally-promiscuous enzyme.     

Reversal of enantioselectivity using tethered bisguanidine catalysts in the aza-Henry reaction

A series of chiral guanidines were synthesized and shown to efficiently catalyze the aza-Henry reaction. Modifications of the catalyst structure revealed important selectivity trends as well as an intriguing reversal in stereoselectivity with bisguanidine variants. These compounds were applied to the aza-Henry reaction between N-Boc imines and nitroalkanes generating the β-nitroamines in up to 77% ee and up to 20:1 diastereoselectivity.     

Electrophilic lactonization as a tool in acyclic stereocontrol. Synthesis of serricornin

Several electrophilic lactonization procedures have been explored as a means of functionalizing olefinic carboxylic acids with relative asymmetric induction, Iodolactonization of δ,? -unsaturated acids under conditions of thermodynamic control exhibits good 1,2- and 1,3-, but not 1,4-induction in the formation of δ-lactones. Mercurilactonization proceeds with good stereocontrol in the formation of both γ- and δ-lactones (1,2-induction), but suffers from the difficulty of elimination during reductive demercuration; phenylselenolactonization with N-(phenylseleno)phthalimide is apparently kinetically controlled, affording high induction with 10, a strongly sterically biased substrate leading to a δ-lactone, but not with 16, which leads to a γ-lactone. In contrast, hydroxymethyllactonization proceeds with good stereocontrol in the case of 26, the ester of 10, but not with the analogous ester of 16. The lactones resulting from cyclization of 10 and 13 were converted in stereospecific fashion into each of the stereoisomers of(±)-serricornin.     

Open-chain remote stereocontrol using allylgermanes

Alk-2-enyl(trialkyl- and -triaryl)germanes are transmetallated by tin(IV) halides at −78 °C with 15 min being sufficient for the transmetallation to proceed effectively to completion. Alk-2-enyl(trialkyl)germanes are transmetallated by both tin(IV) chloride and tin(IV) bromide under these conditions, but the corresponding triphenylgermanes are only transmetallated using tin(IV) chloride. These observations led to procedures for reactions of 5-substituted-pent-2-enyl- and -hex-2-enyl-germanes with aldehydes that proceed with useful levels of 1,5- and 1,6-stereocontrol in favour of the (Z)-1,5-anti- and (Z)-1,6-syn-alkenols, respectively. Slightly improved stereoselectivities were obtained using (Z)-alk-2-enylgermanes. The reaction of (Z)-6-hydroxyhept-2-enyl(triethyl)germane with benzaldehyde when promoted using tin(IV) bromide gave a 3-ethenyl-6-methyl-2-phenyltetrahydropyran rather than the expected homoallylic alcohol.     

1,5-Remote stereocontrol using allylgermanes

Transmetallation of 5- and 4-alkoxypent-2-enylgermanes 8, 10 and 13 using tin(IV) chloride is stereoselective and generates allyltin trichlorides which react with aldehydes with useful levels of 1,5-stereocontrol.     

1,6-Remote stereocontrol using allylgermanes

Transmetallation of 5-hydroxy- and 5-methoxyhex-2-enyl(triethyl)germanes 8 and 9 with tin(IV) bromide is stereoselective and generates allyltin tribromides, which react with aldehydes to give (3Z)-homoallylic alcohols 3 with useful levels of 1,6-syn-stereocontrol.     

Synthesis of (−)-galantinic acid via iterative hydrolytic kinetic resolution and tethered aminohydroxylation

A new synthetic strategy for (−)-galantinic acid is reported using iterative hydrolytic kinetic resolution and tethered aminohydroxylation as the key steps.     

Formal synthesis of ent-dysiherbaine from sulfinyl dihydropyrans by sigmatropic rearrangement and tethered aminohydroxylation

A stereospecific [2,3]-sigmatropic rearrangement of a sulfinyl dihydropyran, followed by a tethered aminohydroxylation reaction, are the key steps of a formal synthesis of ent-dysiherbaine from an enantiopure sulfinyl dienol.