By Sharpless procedure

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

Diketones. The Sharpless procedure for oxidation of alkenes with NaIO catalyzed by Ru02 (11,462-463) is equally efficient for oxidation of alkynes to 1,2-diones. In fact, alkenes and alkynes react at a similar rate, but ether, epoxide, and ester groups are stable to the reagent. A 1-silylacetylene is oxidized to an acylsilane. Yields are moderate to high.1... 

The combination of the preceding method of obtaining allyl alcohols with the Sharpless kinetic resolution (SKR) of secondary allyl alcohols allows conversion of the original racemic allyl alcohol into a pure enantiomer with a 100% theoretical yield. By this procedure, the glycidol obtained by the SKR epoxidation of the secondary allyl alcohol is converted into the corresponding mesylate and then treated with the Te ion, furnishing the allylic alcohol with the same configuration of the enantiomer in the SKR which... 

Oxidation of 338 by the Sharpless procedure 431) gave the chiral epoxide... 

The first observation of the c/x-dihydroxylation reaction with RuO was made by Sharpless et al. in 1976, who noted that E and Z-cyclododecene were oxidised by stoich. RuO /EtOAc/-78 C to the threo and erythro diols [299]. Later RuCyaq. Na(IO )/EtOAc-CH3CN/0 C was used and reaction conditions optimised for many alkenes [300] a useful paper with good practical examples discusses the scope and limitations of the procedure (Table 3.2) [301]. Later oxidations were done with stoich. RuOyaq. acetone/-70 C [302] the same reagent converted A, and A steroids to cw-diols, ketones or acids [303], while RuO /aq. Na(10 )/acetone gave diones and acids [304]. 

The first observation that RuO is usable for the reaction was made by Sharpless et al. in 1976 in a footnote to a paper on osmylation of alkenes. It was found that E- and Z-cyclododecene with stoich. RuO /EtOAc at -78°C gave the threo and erythro diols, but the procedure was not deemed viable owing to the low yields obtained and the necessity for working at low temperatures [157],... 

The epoxidation procedure can also be utilized for the kinetic resolution of secondary allylic alcohols 39 as shown by Sharpless and coworkers (Scheme 59) ". For example, secondary allylic alcohol 39j can be epoxidized very rapidly by using the Sharpless... 

Similar surfactants based upon glucopytanose were synthesized using the Gao and Sharpless procedure for preparation of the cyclic sulfate from methyl a-D-glucopyranoside 252 using a mixture of DMF and ethyl acetate (1 1) as solvent, the axial cyclic sulfite 253 was formed exclusively, as indicated by H NMR spectroscopy, from which the cyclic sulfate 65 was obtained in good yield (Scheme 42) <1999S621>. 

This reaction was used to introduce the final two skeletal carbons in a total synthesis of maytansine (4).2 The reaction of the 2,/ -unsaturated aldehyde (2) with I (R = C6H5) gives the desired 4,5-unsaturated 3-hydroxy ester 3 in 80% yield. The ratio of the desired (S)-alcohol to the epimer is 93 7. The resulting amino acid was cyclized to the lactam in 80% yield with mesitylenesulfonyl chloride (8, 318-319). Epoxidation by the Sharpless procedure (9, 78 79) was also highly stereoselective, giving the desired epoxide and the undesired epimer in the ratio > 200 1. 

In the acetonitrile modification reported by Sharpless and coworkers, hydrolysis t parently does not take place to any tqipreciable extent. Consequently the yield of ester can be significantly increased (equation 11). This improved procedure, along with some minor variants, therefore appears to be the method of choice for effecting the oxidation of ethers with ruthenium tetroxide, and has been widely adopted. 

A simplified work-up procedure has been advanced by Sharpless that removes tartrate from the reaction mixture and destroys the tert-butyl hydroperoxide42. 

A nonaqueous workup is also possible for those substrates that are water soluble. The procedure advanced by Sharpless serves to remove the titanium as its insoluble citrate complex. To the cold reaction mixture is added 30 mM of citric acid monohydrate dissolved in acetone/ diethyl ether (1 9) or 30 mM of citric acid dissolved in diethyl ether42. The cooling bath is removed and the mixture is stirred for 20 - 30 minutes then filtered through a bed of Celite. The filtrate is concentrated to yield the crude epoxy alcohol containing tartrate and rert-butyl hydroperoxide42. 

Among the available methods for introducing an unsaturated carbon-carbon bond into organic molecules, selenoxide elimination reaction has been shown to be quite useful because of its simple procedure and its characteristic regioselec-tivity. Jones et al., who discovered the first selenoxide elimination, proposed an intramolecular mechanism entailing a five-membered ring structure to explain its syn nature [11]. This proposition was shown to be correct by Sharpless et al. who applied the method that was utilized by Cram to determine the stereochemistry of elimination in amine oxides [12]. Thus, the oxidation of erythro-selenide afforded only Z-olefin and that of f/zreo-selenide gave only -olefin (Scheme 4). 

A very utilitarian sequence was developed by Sharpless, using his chiral epoxidation method, to prepare epoxy alcohol 40. Scheme 2.15 depicts the sequence, starting with the inexpensive diene alcohol 38. As pointed out by Sharpless, the original procedure gave poor yields of relatively water-soluble epoxides such as 40, but a modified work-up procedure largely circumvents this difficulty, allowing for direct oxidation of 41 in excellent optical purity. 

Since we wanted to prepare a series of chiral acetylenic sulfoxides with different substituents on the aryl moiety, we needed access to the corresponding chiral sulfinates. Optically pure (-)-menthyl-p-toluenesulfinate (6 a) is commercially available but the other sulfinates (6b and 6c) are not. They were prepared according to an efficient procedure developed by Sharpless [9] from substituted benzenesulfonyl chlorides which are commercially available (Scheme 2). The sulfinates were formed as a mixture of diastereomers by in situ reduction of the... 

Keinan prepared separately the two fragments (the THF moiety and the Y-methyl-y-lactone) and used, as a key step of his sequence, the asymmetric dihydroxylation (AD-mix.-p), the very efficient Sharpless procedure for the formation of a,(3-diols. Then, the cross-coupling was performed by addition of an alkyne and a vinyl halide in the presence of palladium and copper catalysts (Fig. 6). Treatment of the unsaturated ester 48 (prepared in 4 steps from commercially available starting material, and 65 % overall yield) with AD-mix.-p in rerr-butanol/water (1 1) with methanesulfonamide for 16 h at 0 °C afforded the lactone 49 which possessed 3 carbon atoms out of the 4 with the desired absolute configuration. Inversion of the fourth stereocentre after acetonide... 

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