Selectivity Sharpless

Shape anisotropy Shape control Shape factors Shape-memory alloys Shape-selective catalysis Shape selectivity Sharpless catalyst Shaving cream Shaving creams... 

In order to predict facial selectivity, Sharpless and co-workers invoke a mnemonic device.25 To an approaching olefin, the greatest steric constraints are presented by the NW, and to an even greater extent, the SE quadrants. The SW and NE quadrants are more open and, in addition, the SW quadrant contains what is described as an attractive area . The attractive area is particularly well suited to accommodate flat aromatic groups. The olefin positions itself according to the constraints imposed by the ligand and is dihydroxylated from above (p-facc), in the case of dihydroquinidine derivative, or from below (a-face) in the case of dihydroquinine derivatives. The commercially available AD-mix-a and AD-mix-P are chosen according to this mnemonic. 

The synthesis of zaragozic acid A [5] by Nicolaou is summarized in Schemes 3-7. Four of the five stereogenic centers are constructed by two stereo-selective Sharpless dihydroxylations (Scheme 3). In the first, the diene 20, which is synthesized in a few steps from the simple building blocks 15-18, is... 

In a model study towards the synthesis of 4-amino-2,3,6-trideoxyhexoses, the a,P-unsaturated ester 60 and related derivatives proved excellent substrates for enantio- and regio-selective Sharpless asynmietric aminohydroxylation (Scheme IS). ... 

Preparation of Sulfodiimides. The sulfodiimide derived from SES-NH2 has been shown to engage in a diastereofacially selective Sharpless-Kresze type ene reaction with a ring-fused cy-clopentene to give an allylically aminated product (eq 5) that has been exploited in a total synthesis of the marine alkaloid agelastatin... 

Two years later, Ftirstner et al. developed a synthesis of azepine 277 based on a selective Sharpless asymmetric epoxidation of divinylcarbinol (Scheme 2.60) [89]. The resulting epoxide 272 was then regioselectively opened with allylamine to give the corresponding diene. Protection of the secondary amine with an N-Boc group provided the precursor 275 for RCM. CycUzation proceeded in 94% yield using [Mo]-I catalyst (CH2CI2, 30 min, reflux, 94%). Subsequent conversion of the... 

The achiral triene chain of (a//-rrans-)-3-demethyl-famesic ester as well as its (6-cis-)-isoiner cyclize in the presence of acids to give the decalol derivative with four chirai centres whose relative configuration is well defined (P.A. Stadler, 1957 A. Escherunoser, 1959 W.S. Johnson, 1968, 1976). A monocyclic diene is formed as an intermediate (G. Stork, 1955). With more complicated 1,5-polyenes, such as squalene, oily mixtures of various cycliz-ation products are obtained. The 18,19-glycol of squalene 2,3-oxide, however, cyclized in modest yield with picric acid catalysis to give a complex tetracyclic natural product with nine chiral centres. Picric acid acts as a protic acid of medium strength whose conjugated base is non-nucleophilic. Such acids activate oxygen functions selectively (K.B. Sharpless, 1970). 

In the Sharpless epoxidation of divinylmethanols only one of four possible stereoisomers is selectively formed. In this special case the diastereotopic face selectivity of the Shaipless reagent may result in diastereomeric by-products rather than the enantiomeric one, e.g., for the L -(-(-)-DIPT-catalyzed epoxidation of (E)-a-(l-propenyl)cyclohexaneraethanol to [S(S)-, [R(S)-, [S(R)- and [R(R)-trans]-arate constants is 971 19 6 4 (see above S.L. Schreiber, 1987). This effect may strongly enhance the e.e. in addition to the kinetic resolution effect mentioned above, which finally reduces further the amount of the enantiomer formed. 

Both saturated (50) and unsaturated derivatives (51) are easily accepted by lipases and esterases. Lipase P from Amano resolves azide (52) or naphthyl (53) derivatives with good yields and excellent selectivity. PPL-catalyzed resolution of glycidyl esters (54) is of great synthetic utiUty because it provides an alternative to the Sharpless epoxidation route for the synthesis of P-blockers. The optical purity of glycidyl esters strongly depends on the stmcture of the acyl moiety the hydrolysis of propyl and butyl derivatives of epoxy alcohols results ia esters with ee > 95% (30). 

Recently (79MI50500) Sharpless and coworkers have shown that r-butyl hydroperoxide (TBHP) epoxidations, catalyzed by molybdenum or vanadium compounds, offer advantages over peroxy acids with regard to safety, cost and, sometimes, selectivity, e.g. Scheme 73, although this is not always the case (Scheme 74). The oxidation of propene by 1-phenylethyl hydroperoxide is an important industrial route to methyloxirane (propylene oxide) (79MI5501). 

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. 

Figure 1. Stereofacial selectivity rule for the Sharpless asymmetric epoxidation.

The past thirty years have witnessed great advances in the selective synthesis of epoxides, and numerous regio-, chemo-, enantio-, and diastereoselective methods have been developed. Discovered in 1980, the Katsuki-Sharpless catalytic asymmetric epoxidation of allylic alcohols, in which a catalyst for the first time demonstrated both high selectivity and substrate promiscuity, was the first practical entry into the world of chiral 2,3-epoxy alcohols [10, 11]. Asymmetric catalysis of the epoxidation of unfunctionalized olefins through the use of Jacobsen s chiral [(sale-i i) Mi iln] [12] or Shi s chiral ketones [13] as oxidants is also well established. Catalytic asymmetric epoxidations have been comprehensively reviewed [14, 15]. 

Sharpless and co-workers have shown how, with a catalyst developed by Sharpless, the rate and selectivity in a,symmetric epoxidation of allylic alcohols can be improved substantially by using molecular sieve 3 A / 4 A (Gao et al., 1987). In some ca.ses, the use of molecular sieves has allowed asymmetric epoxidation, which was not possible with the original catalyst. 

Figure 3.3 Rationale for predicting the enantiofacial selectivity in Sharpless s dihydroxylation.

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