Allylic alcohols diastereoselectivity

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

In 1963, Dauben and Berezin published the first systematic study of this syn directing effect (Scheme 3.15) [37]. They found that the cyclopropanation of 2-cyclohexen-l-ol 32 proceed in 63% yield to give the syn isomer 33 as the sole product. They observed the same high syn diastereoselectivity in a variety of cyclic allylic alcohols and methyl ethers. On the basis of these results, they reasonably conclude that there must be some type of coordinative interaction between the zinc carbenoid and the substrate. 

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]. 

An interesting way to control the stereoselectivity of metathesis-reactions is by intramolecular H-bonding between the chlorine ligands at the Ru-centre and an OH-moiety in the substrate [167]. With this concept and enantiomerically enriched allylic alcohols as substrates, the use of an achiral Ru-NHC complex can result in high diastereoselectivities like in the ROCM of 111-112 (Scheme 3.18). If non-H-bonding substrates are used, the selectivity not only decreases but proceeds in the opposite sense (product 113 and 114). 

Diastereoselectivity has been observed in oxymercuration of alkenes having nearby oxygen substituents. Terminal allylic alcohols show a preference for formation of the anti 2,3-diols. 

The allylation of carbonyl compounds in aqueous media with SnCl2 can also employ allylic alcohols (Eq. 8.39)84 or carboxylates85 in the presence of a palladium catalyst. The diastereoselectivity of the reactions with substituted crotyl alcohols was solvent dependent. Improved diastereoselectivity was obtained when a mixture of water and THF or DMSO was used, instead of the organic solvent alone. 

Tandem transesterification and diastereoselective intramolecular 1,3-dipolar cycloaddition of a-methoxycarbonylnitrones with chiral allyl alcohols give polycyclic compounds in one step with high stereoselectivity (Scheme 8.14).76 Transition state Ain Scheme 8.14 is more favorable than B because B has severe steric interaction (allylic 1,3-strain).77... 

Photocyclization of benzophenone with chiral allylic alcohols, 9 (R = Me, Et, Pri, and Bu1) is hydroxyl group-directed to give regioselectivity and t/zreo-diastereoselectivity in the formation of mainly 10 <00JA2958>. 

A strategy based on the diastereoselective dipolar cycloaddition reaction of nitrile oxides and allylic alcoholates, has been applied to the synthesis of bis-(isoxazolines) that are precursors to polyketide fragments. These intermediates can be elaborated into protected polyols, for example, 439, by sequential chemos-elective reductive opening of each isoxazoline or, alternatively, by simultaneously, providing access to all stereoisomers of this carbon skeleton (479). 

In the presence of additional unsaturation, the intermediate a-palladium bond formed in these transformations can undergo a further Heck process to establish an additional C-C bond. The reactions of allylic alcohols with vinyl ethers proceed along this pathway and lead diastereoselectively to THFs (Equation (112)), with Cu(OAc)2409 and 02410 used as the stoichiometric oxidants. This methodology has been used to good effect in the syntheses of (—)-dihy-droxanthatin,409 fraxinellone limonoids,411 and mycalamide A.412... 

An interesting variant involves the use of an allylic alcohol as the alkene component. In this process, re-oxidation of the catalyst is unnecessary since the cyclization occurs with /Uoxygen elimination of the incipient cr-Pd species to effect an SN2 type of ring closure. Both five- and six-membered oxacycles have been prepared in this fashion using enol, hemiacetal, and aliphatic alcohol nucleophiles.439,440 With a chiral allylic alcohol substrate, the initial 7r-complexation may be directed by the hydroxyl group,441 as demonstrated by the diastereoselective cyclization used in the synthesis of (—)-laulimalide (Equation (120)).442 Note that the oxypalladation takes place with syn-selectivity, in analogy with the cyclization of phenol nucleophiles (1vide supra). 

The configuration of the product in diastereoselective hydrogenation -whether 1,2-syn or 1,2-anti - is related to the substitution pattern of the starting alkene. The allyl alcohol with a 1,1-disubstituted olefin unit affords the antiproduct, while the syn-product is formed from the allyl alcohol with a trisubsti-tuted olefmic bond (Table 21.8, entries 6-9). The complementarity in diastereoselective hydrogenation of di- and tri-substituted olefins may be rationalized based on the conformation analysis of the intermediary complex (Scheme 21.1)... 

With an increase of conversion, the enantiopurity of unreacted (S)-substrate increases and the diastereoselectivity of the product decreases. Using Ru-((S)-binap)(OAc)2, unreacted (S)-substrate was obtained in more than 99% ee and a 49 1 mixture of anti-product (37% ee (2R,iR)) at 76% conversion with a higher kR ks ratio of 16 1 [46]. In the case of a racemic cyclic allyl alcohol 24, high enantiopurity of the unreacted alcohol was obtained using Ru-binap catalyst with a high kR ks ratio of more than 70 1 [Eq. (16)] [46]. In these two cases, the transition state structure is considered to be different since the sense of dia-stereoface selection with the (S)- or the (R)-catalysts is opposite if a similar OH/ C=C bond spatial relationship is assumed. 

In Sharpless epoxidation reactions, (Z)-substituted allylic alcohols react much more slowly than the corresponding (E )-substituted substrates, and sometimes the reaction is sensitive to the position of preexisting chirality in the selected substrate. For instance, in the presence of (+)-DET, chiral (E)-allylic alcohol 10 undergoes epoxidation in 15 hours to give product 11 as the major product with a diastereomeric ratio of >20 1. As for reaction with ( )-DET, 12 is then obtained, also with a diastereoselectivity of >20 1 (Scheme 4-4). 

It is also possible to carry out a substrate-controlled reaction with aldehydes in an asymmetric way by starting with an acetylene bearing an optically active ester group, as shown in Eq. 9.8 [22]. The titanium—acetylene complexes derived from silyl propiolates having a camphor-derived auxiliary react with aldehydes with excellent diastereoselectivity. The reaction thus offers a convenient entry to optically active Baylis—Hillman-type allyl alcohols bearing a substituent (3 to the acrylate group, which have hitherto proved difficult to prepare by the Baylis—Hillman reaction itself. 

Coupling of vinyl iodides with aldehydes (12, 137). Further study1 of this 1,2-addition of alkenylchromium compounds to aldehydes to form allylic alcohols indicates that the reaction is applicable to a-alkoxy and a,(i-bisalkoxy aldehydes by use of a solvent other than DMF, which can promote elimination to an enal. A wide number of other functional groups can also be accommodated. Both vinyl iodides and p-iodo enones can be used as precursors to the alkenylchromium reagent. The reaction is only modestly diastereoselective, but the stereochemistry of a disubstituted vinyl iodide is retained. 

Cyclopropanation.1 The carbenoid obtained from the reaction of CH2I2 with Sm or Sm/Hg in THF effects cyclopropanation of ally lie alcohols, but not of isolated double bonds. The reaction of both cyclic and acyclic allylic alcohols proceeds in generally high yield and often with marked diastereoselectivity. 

The highly chemo-, regio-, and diastereoselective and stereospecific epoxidation of various allylic alcohols with only 1 equivalent of hydrogen peroxide in water solvent could be efficiently catalyzed by an isolated dinuclear peroxotungstate [W203(02)4(H20)2]2 [93,94] ... 

However, styrene and cyclohexene gave complex product mixtures, and 1-octene did not react under the same reaction conditions. Thus, the activity of this catalyst is intrinsically low. Jacobs and co-workers [159,160] applied Veturello s catalyst [PO WCKOj ]3- (tethered on a commercial nitrate-form resin with alkylammonium cations) to the epoxidation of allylic alcohols and terpenes. The regio- and diastereoselectivity of the parent homogeneous catalysts were preserved in the supported catalyst. For bulky alkenes, the reactivity of the POM catalyst was superior to that of Ti-based catalysts with large pore sizes such as Ti-p and Ti-MCM-48. The catalytic activity of the recycled catalyst was completely maintained after several cycles and the filtrate was catalytically inactive, indicating that the observed catalysis is truly heterogeneous in nature. 

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