Sharpless osmylation

Prior to our work, Hawkins and Meyer had performed the kinetic optical resolution of the inherently chiral fiillerene D2-C76 by employing the asymmetric Sharpless osmylation reaction [17]. A comparison of the circular dichroism (CD) spectra reported by I wkins and Meyer for the C76 enantiomers that they obtained [17] to those of a variety of optically active, covalent derivatives of C76, prepared by us [18] revealed a large, unexpected difference in the magnitude of the Cotton effects. Whereas our covalent C76 derivatives displayed bands reaching Ae values up to 250 M cm , the enantiomers of the pure hillerenes reported by Hawkins and Meyer displayed bands widi Ae values up to only 32 M cm [17, 19]. In order to reinvestigate the chiroptical... 

The interest in asymmetric synthesis that began at the end of the 1970s did not ignore the dihydroxylation reaction. The stoichiometric osmylation had always been more reliable than the catalytic version, and it was clear that this should be the appropriate starting point. Criegee had shown that amines, pyridine in particular, accelerated the rate of the stoichiometric dihydroxylation, so it was understandable that the first attempt at nonenzymatic asymmetric dihydroxylation was to utilize a chiral, enantiomerically pure pyridine and determine if this induced asymmetry in the diol. This principle was verified by Sharpless (Scheme 7).20 The pyridine 25, derived from menthol, induced ee s of 3-18% in the dihydroxylation of /rcms-stilbene (23). Nonetheless, the ee s were too low and clearly had to be improved. 

Greg Fu supervised the proofreading and provided the structural formula based on the x-ray data for the new Sharpless catalytic reagent for osmylation of alkenes. Martita F. Barsotti is the photographer for the picture of some present and former co-workers for Reagents. 

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 Sharpless epoxidation (eq. 5)23 may be performed both stoichiometrically and catalytically with high asymmetric induction, whereas the complementary osmylation (eq. 6)24 is performed in the catalytic version. 

Salinosporamide synthesis 196 Sharpless asymmetric dihydroxylation (see also Osmylation) 84,89, 141, 189 Sharpless asymmetric epoxidation 32,141 Silane, allylic synthesis 43 Sonogashira coupling (see Pd)... 

An asymmetric osmylation method has been developed by Sharpless and coworkers. 0s04 modified by a dihydroquinidine auxiliary (cinchona alkaloid derivatives)449,455 158 or chiral diamines449,457 160 such as 59 and 60 used in stoichiometric oxidation may yield cis diols with excellent optical purity 460... 

The selective oxidation of hydrocarbons, particularly that of alkanes, remains a challenge. It is not surprising, therefore, that the problems of oxidation processes are addressed in several books,1043-1045 reviews,1046-1057 and a journal special issue,1058 as well as in international conferences1059-1064 devoted to the topic. For the advances in chirally catalyzed oxidation processes, including asymmetric epoxidation and osmylation, Sharpless was one of the recipients of the 2001 Nobel Prize in Chemistry. 

The [2+2] Mechanism Already in 1977 Sharpless proposed a stepwise [2+2] mechanism for the osmylation of olefins in analogy to related oxidative processes with d°-metals such as alkene oxidations with CrO,Cl2 [23, 24], Metallaoxetanes [25] were suggested to be formed by suprafacial addition of the oxygens to the olefinic double bond. In the case of osmylation the intermediate osmaoxetane would be derived from an olefm-osmium(VIII) complex that subsequently would rearrange to the stable osmium(VI) ester. 

Corey also pointed out that 16 reflects the transition-state of an enzyme-substrate complex. Its formation was later supported by the observation of Michaelis-Menten-type kinetics in dihydroxylation reactions and in competitive inhibition studies [37], This kinetic behavior was held responsible for the non-linearity in the Eyring diagrams, which would otherwise be inconsistent with a concerted mechanism. Contrary, Sharpless stated that the observed Michaelis-Menten behavior in the catalytic AD would result from a step other than osmylation. Kinetic studies on the stoichiometric AD of styrene under conditions that replicate the organic phase of the catalytic AD had revealed that the rate expression was clearly first-order in substrate over a wide range of concentrations [38],... 

In 1977, Sharpless proposed the intermediacy of a four-membered metal-lacycle in the oxidation of cyclododecene by Cr02Cl2.60 This was an attempt to explain a minor but primary product, in which an oxygen and a chlorine were added in a syn fashion to one face of the /3-bond. Later, this type of intermediate was incorporated into a new mechanism for osmylation,61 in which an initial [2 + 2] cycloaddition led to an osmaoxetane which in a second step underwent ring expansion to form the observed metal diolate product. At the time, the [2 + 2] process was viewed as a violation of orbital symmetry rules, and it was not until the extensive work in the 1970s and 1980s on cycloadditions to metal carbenes that a theoretical basis for such a process allowed its broader acceptance. 

In the concluding steps, manipulation of the furan ring of 89 gave 90 as a mixture of positional isomers. These were collectively converted to the unsaturated diol 91. The last crucial step, installation of two hydroxyl groups on the double bond, was achieved using a standard osmylation reaction [84]. In a second approach for the same step, the Sharpless asymmetric dihydroxylation of 91 was used and yielded one diastereoisomer 92 almost exclusively [85]. This second approach concluded with the synthesis of a lactone containing all correct stereocenters of the squalestatin core with the exception of that at C6. 

Two classes of ligands have been successfully used in asymmetric osmylation of prochiral olefins chiral diamines and cinchona alkaloids. The diamines have been developed mainly by Corey, Koga and Tomioka, Hirama and their coworkers [559, 750, 754, 755, 756], and cinchona alkaloids have been designed and implemented by Sharpless and coworkers [750, 753-756],... 

According to Sharpless, two cycles operate in the catalytic reaction (Scheme 39) (88c, 90). The first cycle is highly enantioselective, whereas the second is poorly enantioselective. Hydrolysis of the key intermediate formed from B and oxidant is not very fast. The second osmylation of olefinic substrate occurs as the intermediate enters the undesired catalytic cycle. Therefore, slow addition of olefinic substrates to minimize the second cycle is essential for obtaining high ee. Use of potassium hexacyanoferrate(III) as oxidant in a 1 1 ferf-butyl alcohol-water two-layer system can suppress the second cycle and lead to high enantioselectivity (91). This procedure allows the convenient synthesis of (8-lactams from 2-octenoate. 

Since cis-3, trans-3, and trans-2 bis-adducts of 50 with identical addends are chiral as a result of inherently chiral functionalization patterns [10, 44-46], it was of interest to explore whether Bingel macrocyclizations with bismalonates bridged by non-racemic tethers would provide an enantioselective synthesis of these compounds. An overall enantioselective synthesis of optically active Cgg bis-adducts had been achieved previously by asymmetric Sharpless bis-osmylation [77] however, this sequential bis-func-tionalization lacks the regioselectivity of the Bingel macrocyclization, and therefore requires tedious regioisomer separations. 

Acyclic Alditols. - Brimacombe s group have published full details of their work on the stereoselective synthesis of higher sugars, some of which is covered in Chapter 2 other papers describe the Sharpless oxidation of the octose derivative (1) to give the oxiran (2), and hence the D-erythro isomer (3), osmylation... 

A full account has been given of the work by Brimacombe s group (see Vol. 23, p. 9) on the formation of octuronic acid derivatives by catalytic osmylation of a,p-unsaturated esters in the presence of Sharpless chiral ligands, where double asymmetric induction can be used to enhance the Kishi selectivity.66 The trehalose derivative (44) could be homologated to the bis-uronic acid (45) using a carbonyl insertion procedure (Scheme 13), as well as by use of the reaction of cyanide ion on the ditriflate analogous to (44)67... 

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