Sharpless protocol

The trisubstituted alkene of 10 was more readily oxidized than was the congested tetrasubstituted alkene, so the more reactive alkene was temporarily epoxidized. After ozonolysis, the epoxide was reduced off using the Sharpless protocol. It is a tribute to the specificity of this reagent that the easily-reduced a-acetoxy ketone is not affected. Selective silylation of the more accessible ketone followed by melhylenation, hydrolysis and addition of methyl lithium to the outside face of the previously protected carbonyl then delivered 1. 

DIBAH reduction of 4 at -78 °C provides the corresponding trans-allylic alcohol. Successive epoxidation with meto-chloroperbenzoic acid (MCPBA) yields a single syn epoxide 5. The stereochemical assignment is proven by a second experiment using the asymmetric Sharpless epoxidation protocol. Both MCPBA and the Sharpless protocol using (-)-diethyl D-tartrate provided 5. 

Although no specific synthesis uses a carbohydrate-type synthon that has been prepared by an asymmetric oxidation, the methodology offers many advantages over a synthesis starting from a carbohydrate (Chapter 4). The useful building block 3 is available by a Sharpless protocol (Scheme 9.8).92... 

Ordinary alkenes (without an allylic OH group) do not give optically active alcohols by the Sharpless protocol because binding to the catalyst is necessary for enantioselectivity. Simples alkenes can be epoxidized enantioselectively with sodium hypochlorite (NaOCl, commercial bleach) and an optically active manganese-complex catalyst. An important variation of this oxidation uses a manganese-salen complex with various oxidizing agents, in what is called... 

The alcohol was protected as its TMS ether, and the C-15,16 alkene stereospecifically dihydroxylated to give compound 50. The diol was then converted to its cyclic sulfate derivative according to the Sharpless protocol.29 Attempted base-catalyzed elimination of the sulfate to introduce the C-14,15 alkene was plagued by side-reactions involving epoxide formation by displacement of the sulfate by the adjacent TMS ether, perhaps aided by enolization of the methyl ketone. Instead, displacement of the sulfate by iodide ion occurred uneventfully to provide 51 as its tetrabutylammonium salt. 

Dihydroxylation. Besides the enormously popular and effective cinchona alkaloid-based chiral auxiliaries several C2-symmetrical diamines (13), (14) and (15) have been developed to direct alkene dihydroxylation with OSO4. These efforts are probably overwhelmed by the Sharpless protocols because the approaches are not catalytic with respect to the most expensive and toxic reagent. 

Distereoselective dihydroxylation of the C-13 cinnamoyl derivative 8.6.16 was carried out using the Sharpless protocol, and provided the desired (2 R,3 S) diol as the major product in a 4 1 ratio. Conversion of the 2 -triethylsilyl derivative of the diol derived from... 

Another modification of Route B requires enantioselective reduction of ketones (E)-27 or stereoselective carbon-carbon bond formation at C-1 of (E)-27 (R = H) with appropriate organometallic species in the presence of chiral additives, both of which successfully supply the optically active (E)-26. The resulting chiral allylic alcohols (E)-26 are subjected to hydrogen bond-directed epoxidation with mCPBA, leading to the diastereoselective formation of syn-epoxy alcohols. In conplementary fashion, antz-selective epoxidation is possible using the Sharpless protocol. ... 

First, we selected 3a as the first synthetic target. The synthetic procedures used are outlined in Schemes 3 and 4. Asymmetric epoxidation of the allyl alcohol 4 by the Sharpless protocol [15] provided 5, which had 6S and IS chiral centers that corresponded to those of 3a. Regioselective epoxidation of 5 with /M-chloroperbenzoic acid exclusively gave the diepoxide 6 as a diastereomeric mixture. The primary hydroxyl group of 6 was converted to its triflate, with... 

The Sharpless-Katsuki asymmetric epoxidation reaction (most commonly referred by the discovering scientists as the AE reaction) is an efficient and highly selective method for the preparation of a wide variety of chiral epoxy alcohols. The AE reaction is comprised of four key components the substrate allylic alcohol, the titanium isopropoxide precatalyst, the chiral ligand diethyl tartrate, and the terminal oxidant tert-butyl hydroperoxide. The reaction protocol is straightforward and does not require any special handling techniques. The only requirement is that the reacting olefin contains an allylic alcohol. 

Another interesting application of the deoxygenation reaction is shown in Scheme 12.6. Sharpless epoxides are transformed to enantiomerically pure allylic alcohols [14]. It should be noted that the disadvantage of the loss of one-half of the allylic alcohol, as in the case of kinetic resolutions of allylic alcohols, is not a problem when this protocol is employed. 

The asymmetric dihydroxylation protocol was the second massive contribution by Professor Barry Sharpless to synthetic organic chemistry. The first procedure, introduced with Katsuki, involves the catalytic asymmetric epoxida-tion of allylic alcohols. A typical example is shown in Scheme 17, wherein ( )-allylic alcohol (23) is epoxidized with tert-b utyl hyd roperox ide, in the presence of titanium tetra-isopropoxide and optically active diethyl tartrate to give the... 

Prior to the usage of the Ti-based catalytic system , the Sharpless group had reported their first asymmetric epoxidation of allylic alcohols using a combination of VO(acac)2/ TBHP and the chiral hydroxamic acid 67 (ee < 50%) or derivatives (ee 80%) ". In 1999, Yamamoto and coworkers described an improvement of this oxidation protocol, ee values up to 94%, by using hydroxamic acids derived from binaphthol, 68 being the... 

More recently, in light of the development of the Sharpless asymmetric dihydroxylation protocol [20], we have approached the synthesis of diols such as 14 (Scheme 2) from the alkene. Thus, treatment of the alkenyl D-glucosides 15 vmder the conditions of the Sharpless dihydroxylation gave a range of diols 16 with varying diastereoisomeric excesses (Table 1). One of these mixtures of diols, upon recrystallization, yielded the pure diastereoisomer, namely the diol 14. This procedure now gives a very rapid and efficient entry into one of the precursor diols for the synthesis of the optically-pure epoxides [21]. 

With a twist on the Sharpless asymmetric epoxidation protocol, Yamamoto and co-workers <99JOC338> have developed a chiral hydroxamic acid (17) derived from binaphthol, which serves as a coordinative chiral auxiliary when combined with VO(acac)j or VO(i-PrO)j in the epoxidation of allylic alcohols. In this protocol, triphenylmethyl hydroperoxide (TiOOH) provides markedly increased enantiomeric excess, compared to the more traditional t-butyl hydroperoxide. Thus, the epoxidation of E-2,3-diphenyl-2-propenol (18) with 7.5 mol% VO(i-PiO)3 and 15 mol% of 17 in toluene (-20 °C 24 h) provided the 2S,3S epoxide 19 in 83% ee. 

The development of asymmetric cyclopropanation protocols has been actively studied and in recent years remarkable progress has been made. The extent of chiral induction that can now be obtained in these reactions approaches the level of other classic catalytic asymmetric reactions on alkenes, such as catalytic hydrogenation and the Sharpless epoxidation.37... 

Corey used the Sharpless dihydroxylation protocol. Which reagents are necessary ... 

A variation within the osmium-catalysed asymmetric dihydroxylation (AD) of alkenes has been described that yields cyclic boronic esters from alkenes in a straightforward manner. A protocol based on the Sharpless AD conditions (for enantiose-lective oxidation of prochiral olefins) has been developed that gives cyclic boronic esters, rather than free diols, with excellent enantiomeric excesses. Some of the... 

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