Prochiral allylic alcohols

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) ... 

Overman LE, Owen CE, Pavan MM, Richards CJ (2003) Catalytic asymmetric rearrangement of allylic N-aryl trifluoroacetimidates. A useful method for transforming prochiral allylic alcohols to chiral allylic amines. Org Lett 5 1809-1812... 

Enantiofacial selectivity in the epoxidation of prochiral allylic alcohols (allylic alcohol drawn as it is shown OH down at the right side)... 

More than a decade of experience on Sharpless asymmetric epoxidation has confirmed that the method allows a great structural diversity in allylic alcohols and no exceptions to the face-selectivity rules shown in Fig. 10.1 have been reported to date. The scheme can be used with absolute confidence to predict and assign absolute configurations to the epoxides obtained from prochiral allylic alcohols. However, when allylic alcohols have chiral substituents at C(l), C(2) and/or C(3), the assignment of stereochemistry to the newly introduced epoxide group must be done with considerably more care. 

Indeed, several interesting procedures based on three families of active catalysts organometallic complexes, phase-transfer compounds and titanium silicalite (TS-1), and peroxides have been settled and used also in industrial processes in the last decades of the 20th century. The most impressive breakthrough in this field was achieved by Katsuki and Sharpless, who obtained the enantioselective oxidation of prochiral allylic alcohols with alkyl hydroperoxides catalyzed by titanium tetra-alkoxides in the presence of chiral nonracemic tartrates. In fact Sharpless was awarded the Nobel Prize in 2001. 

In the presence of a cationic Rh[((/ )-binap)(cod)] complex, geranyl or neryl amides isomerize slowly to give a mixture of the corresponding enamide and dienamide (Scheme 20) (2). The optical purity of the chiral enamide is high, but the chemical yield is low. Certain cyclic allylic amides give the enamide isomers in a high ee. With a DIOP-Rh catalyst, prochiral allylic alcohols are converted to optically active aldehydes with low ee (31). 

The enantioselectivity principles portrayed in Figure 6A.1 have been followed without exception in all epoxidations of prochiral allylic alcohols reported to date, and one may use these principles to assign absolute configurations to the epoxy alcohols prepared by the method. On the other hand, epoxidation of allylic alcohols with chiral substituents at C-l, C-2, and/or C-3 does not always follow these principles, and assignment of absolute configuration to the products must be made with care. Even in the latter cases, reliable assignments usually can be made if the outcome (diastereomeric ratio) of epoxidation with both the (+) and (-)-tartrate ester ligands is compared. 

The Sharpless Epoxidation allows the enantioselective epoxidation of prochiral allylic alcohols. The asymmetric induction is achieved by adding an enantiomerically enriched tartrate derivative. 

Enantioselectivity. In 1980, T. Katsuki and K. B. Sharpless (Nobel Prize, 2001) reported a method whereby prochiral allylic alcohols are epoxidized in the presence of r-BuOOH, Ti(/-OPr)4, and (-h)-or (-)-diethyl tartrate (DET) with high regio- and stereoselectivity to produce the corresponding optically active epoxides." ... 

Alcohols can be obtained from many other classes of compounds such as alkyl halides, amines, al-kenes, epoxides and carbonyl compounds. The addition of nucleophiles to carbonyl compounds is a versatile and convenient methc for the the preparation of alcohols. Regioselective oxirane ring opening of epoxides by nucleophiles is another important route for the synthesis of alcohols. However, stereospe-cific oxirane ring formation is prerequisite to the use of epoxides in organic synthesis. The chemistry of epoxides has been extensively studied in this decade and the development of the diastereoselective oxidations of alkenic alcohols makes epoxy alcohols with definite configurations readily available. Recently developed asymmetric epoxidation of prochiral allylic alcohols allows the enantioselective synthesis of 2,3-epoxy alcohols. 

The chiraUy modified cluster HRu3(CO)10(i -OCNCH2CH2CH2CHCH2 OCH3) catalyzes the conversion of the prochiral allylic alcohol nerol (78) into the chiral aldehyde citronellal (79)... 

The Sharpless epoxidation converts a prochiral allylic alcohol 1 into a chiral epoxy alcohol 2 and gives that epoxy alcohol with a very high enantiomeric excess. 

In 1976 the first example of the asymmetric isomerization of prochiral allyl alcohols to aldehydes was reported [26]. The isomerization proceeds by migration of the olefinic double bond of allyl alcohol 12 from the 2,3 position to the 1,2 position to give enol 13, which transforms rapidly to aldehyde 14 (Scheme 2). It was claimed that DIOP (15)-modified rhodium catalysts (Fig. 1) exemplified the enantiorecognition in 2 to 4% ee. After their successful use for allylamines, BINAP (16)-coordinated rhodium catalysts (Fig. 1) were applied for the isomer-... 

Synthesis of Chiral Oxirans. The recently introduced Katsuki-Sharpless reagent (titanium alkoxide with tartrate) has proved highly effective for the maiden introduction of chirality into prochiral allylic alcohols. An interesting development of this procedure has afforded the possibility of kinetic resolution of racemic allylic alcohols. The basis of the method involves the... 

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