| Three chiral salen-based transition-metal complexes are used as asymmetric catalysts in two reactions--an epoxidation employing a Mn catalyst and epoxide opening reactions utilizing Cr and Co catalysts. All of these metal-catalyzed reactions are shown to be efficient, powerful tools for organic synthesis, employing low catalyst loadings {dollar}({lcub}le{rcub}5{dollar} mol%), straightforward procedures, and providing useful chiral building blocks with high enantioselectivity.; The scope of the (salen)Mn(III)-catalyzed asymmetric epoxidation (AE) reaction of unfunctionalized olefins has been expanded to include trisubstituted and tetrasubstituted olefins. These new substrates are epoxidized with high enantioselectivities (up to 97% ee) and good yields. The results obtained from these two substrate classes have also given rise to new mechanistic insights into how the olefin approaches the reactive (salen)Mn(V)(oxo) species, leading to a better understanding of this reaction. The synthetic utility of the products obtained from the epoxidation of trisubstituted olefins has been demonstrated with the synthesis of two important chiral auxiliaries.; The regioselective ring opening of enantiomerically enriched epoxides with {dollar}rm TMSNsb3{dollar} catalyzed by a chiral {dollar}rm (salen)Cr(III)Nsb3{dollar} complex has also been investigated. By applying a chiral catalyst to an optically active substrate, it is possible to direct nucleophilic attack at either epoxide carbon through an unusual type of double stereoselection. Regioselectivities greater than 100:1 have been obtained, and this methodology has been applied to the efficient synthesis of (1S,2S)-norpseudoephedrine, an anorexiant.; The hydrolytic kinetic resolution (HKR) of styrene oxide derivatives catalyzed by a chiral (salen)Co(III) complex has also been investigated. This asymmetric reaction allows in facile access to a variety of highly enantioenriched styrene oxide derivatives (up to 99% ee) which are important building blocks for the preparation of several pharmaceutically significant compounds. One derivative in particular, 3-chlorostyrene oxide, is a key intermediate for the preparation of several {dollar}beta{dollar}-3-adrenergic compounds that exhibit antiobesity and antidiabetic therapeutic properties. In addition to 3-chlorostyrene oxide, a variety of derivatives (H, 4-Cl, 3-{dollar}rm NOsb2){dollar} have been synthesized via a tandem asymmetric epoxidation-hydrolytic kinetic resolution sequence. Starting from racemic 3-methoxystyrene oxide, HKR has been used in the synthesis of a bronchial dilator and antiasthmatic agent, (R)-phenylephrine hydrochloride. |
