Allylic alcohols diastereoselective asymmetric reactions

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. 

Scheme 8 summarizes the introduction of the missing carbon atoms and the diastereoselective epoxidation of the C /C double bond using a Sharpless asymmetric epoxidation (SAE) of the allylic alcohol 64. The primary alcohol 62 was converted into the aldehyde 63 which served as the starting material for a Horner-Wadsworth-Emmons (HWE) reaction to afford an E-configured tri-substituted double bond. The next steps introduced the sulfone moiety via a Mukaiyama redox condensation and a subsequent sulfide to sulfone oxidation. The sequence toward the allylic alcohol 64 was com-... 

Achiral ester-substituted nitrones as well as chiral nitrones can be employed in diastereoselective asymmetric versions of tandem transesterification/[3 + 21-cycloaddition reactions, as shown in Scheme 11.54 (174). High diastereoselectivity and excellent chemical yields have been observed in the reaction with a (Z)-allylic alcohol having a chiral center at the a-position in the presence of a catalytic amount of TiCl4- On the other hand, the reaction with an ( )-allylic alcohol having a chiral center at the a-position, under similar conditions, affords very low selectivities. Tamura et al. has solved this problem with a double chiral induction method. Thus, high diastereoselectivity has been attained by use of a chiral nitrone. 

Sato and coworkers have reported an asymmetric synthesis of Baylis-Hillman-type allylic alcohols 48, 49 via a chiral acetylenic ester titanium alkoxide complex (Scheme 9) [41]. These reactions rely on the use of the novel acetylenic ester titanium alkoxide complex 44 with a camphor-derived chiral auxiliary. Optically active, stereodefined hydroxy acrylates 46, 47 were obtained in high yields and with excellent regio- and diastereoselectivities. The chiral auxiliary was subsequently cleaved off by alcoholysis. 

In this chapter, recent applications of (W)-phcnylglycine amide (1) in asymmetric synthesis are presented (Figure 25.2). The first section deals with diastereoselective Strecker reactions for the preparation of a-amino acids and derivatives, whereas the second section focuses on diastereoselective allylation of imines for preparation of enantiomerically pure homoallylamines. This latter class of compounds is a well-known intermediate for the synthesis of, for example, many types of amines, amino alcohols, and P-amino acids. The final section describes reduction of imines providing enantiomerically pure amines. (S)-3,3-Dimethyl-2-butylamine and (S)-l-aminoindane will be presented as leading examples. The results described in this chapter originate from a longstanding cooperation in the field of chiral technology development between DSM Pharma Chemicals and Syncom B.V. 

Sharpless asymmetric epoxidation ° is an enantioselective epoxidation of an allylic alcohol with ferf-butyl hydroperoxide (f-BuOOH), titanium tetraisopropoxide [Ti(0-fPr)4] and (-b)- or (—)-diethyl tartrate [(-b)- or (—)-DET] to produce optically active epoxide from achiral allylic alcohol. The reaction is diastereoselective for a-substituted allylic alcohols. Formation of chiral epoxides is an important step in the synthesis of natural products because epoxides can be easily converted into diols and ethers. 

Walsh and co-workers have developed a one-pot method for the synthesis of hydroxyepoxides via an initial synthesis of an allylic alcohol followed by an asymmetric epoxidation <05JOC1262,05JA14668,05JA16416>. This reaction provides an improvement in overall yields over the typical kinetic resolution reaction. The method involves an initial asymmetric addition to the aldehyde followed by a diastereoselective epoxidation reaction. 

Scheme 8.8. Reactions of a chiral allylic alcohol under Sharpless epoxidation conditions (Ti(0-i-Pr)4, /-BuOOH) using the chiral tartrates given (DIPT = diisopropyltartrate). (a) The matched case, in which the preferred approach of the asymmetric catalyst and the diastereoselectivity of the substrate are the same, (b) The mismatched case, (cj An example of a Sharpless kinetic resolution (KR).

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