Asymmetric reactions osmylation

Certain tertiary amines such as pyridine or a-quinuclidine accelerate the stoichiometric reaction between osmium tetroxide and olefins (86). An asymmetric olefin osmylation using stoichiometric amounts of cinchona alkaloids as the chiral ligands was described in 1980 (87a). Optical yields of up to 90% were attained with frans-stilbene as substrate. 

Asymmetric catalytic osmylation (14, 237-239 15, 240-241 16, 249). In the early versions of this reaction the asymmetry was obtained by use of esters of dihydroqui-ninc and dihydroquinidine as ligands. Markedly higher enantiosclcctivity obtains by use of ligands 1 and 2, prepared by reaction of 1,4-dichlorophthalazinc with dihydroquinidine (ligand 1) and dihydroquininc (ligand 2). ... 

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. 

Enantiomencally pure (+)- and (-)-diphenylethylenediamines have recently been used for highly stereoselective Dlels-Alder, aldol,8 allylation,9 osmylation,10 and epoxidafion11 reactions. Other synthetic applications involve enantioselective Michael addition12 and asymmetric hydrogenation.13... 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

Substituted 4,5-dihydro-5-vinylisoxazoles (40), obtained by regio- and stereospecific cycloaddition of nitrile oxides to dienes, undergo smooth osmium-catalyzed c/s-hydro-xylation to give amino-polyol precursors (equation 28)45. The reaction is anti selective, the diastereomeric ratios ranging from 73 27 up to 99 1. Highest stereoselectivities were observed when R3 was methyl. Thus, whereas osmylation of 40a afforded a 78 22 mixture of 41a and 42a, respectively, in 80% overall yield, similar treatment of 40b resulted in a 92 8 mixture of 41b and 42b, respectively, in 70% overall yield. The cycloaddition-osmylation sequence allows control of the relative configuration of up to 4 contiguous asymmetric centers. 

Asymmetric dihydroxylation of alkenes (14, 235-239). Further study1 of this reaction reveals that the optical yields of products can be markedly improved by slow addition (5-26 hours) of the alkene to the catalyst in acetone-water at 0° with stirring. The enantioselectivity can also be increased by addition of tetraethylam-monium acetate, which facilitates hydrolysis of osmate esters. The report suggests that the first product (1) of osmylation can undergo a second osmylation to provide 2, with reverse enantioselectivity of the first osmylation. 

Genisson et al. also prepared two diastereomers of 2 -hydroxymethyl analogs through an asymmetric Baylis-Hillman reaction-like sequence to prepare a A-substimted 2 -methylene C-13 side chain (Scheme 3-3). After incorporation of the side chain to C-13 of 7,10-ii/-Troc-10-DAB, the product was then subjected to osmylation to yield 2 (R)- and 2 (5)-hydroxymethyl docetaxel 7a-b analogs stereoselectively. Both taxoids displayed less tubulin polymerization abilities than did paclitaxel, but the major product 2 / -isomer 7a is more active than the minor one 2 5-isomer 7b. ... 

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. 

Figure 8.4. Representative ligands used in stoichiometric, asymmetric dihydroxylation reactions, (a) Dihydroquinidine (DHQD) and (b) dihydroquinine (DHQ) are used for stoichiometric osmylation reactions when R = H effective dihydroxylation catalysts result from appropriate modifications at this position (e.g., see Figure 8.5 below). Also, (c) [69] and (d) [70] are examples of C2 symmetrical ligands used in stoichiometric reactions.

When n = 3 or 4, these ligands suppress the reaction completely. If R is an acyl group, the cnantiosclcctivity is depressed. These ligands (I) can also effect asymmetric osmylation of mono- and disubstituted terminal alkencs, but not of civ-disubstituted alkcncs. 

Asymmetric monodihydroxylation of 1,3-dienes. This osmylation can be effected with use of [l,4-bis(9-0-dihydroquinidinyl)phthalazinc (1) as the ligand. In this reaction the products with few exception are ene diols generally osmylation occurs with the more electron-rich double bond. Some regiosclcctivity is observed with nonconjugatcd dienes, with a preference for trisubstituted double bonds over terminal ones. 

This desilylation provides a key step in an asymmetric osmylation of a double bond joined by one carbon to a five-memberd siloxane. Thus the aldehyde 3, obtained by deprotection of a (H2,Pd/C) and Swern oxidation, undergoes a Wittig-Horner reaction to provide the unsaturated amide 4 in 70% overall yield. This product undergoes osmylation to give essentially one product (5). After protection of the two hydroxy groups, the... 

Tarchonanthuslactone (27) has been isolated from a compositae, tarchonanthus trilobus (57). All of the known syntheses of optically active 27 reported thus far involve substrate-control and >14 steps (58-61). Our 7-step reagent-controlled asymmetric synthesis begins with the allylboration of acetaldehyde, followed by osmylation, periodate cleavage, a second allylboration, esterification, and ring-closing metathesis reaction sequence (Scheme 9). 

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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