Stereoselective intramolecular reductive

A high-yielding stereoselective intramolecular reductive etherification of the 5-silyloxy substituted ketone 310 provides the final step in a total synthesis of the antibiotic (—)-centrolobine 311 (Equation 134) <2003OL3883>. 

Keto-alcohols 149 participated in a stereoselective intramolecular reductive etherification process to afford differentially substituted 1,4-oxazepanes 150 in mosdy good yields with excellent diastereoselectivities. In a single example, the use of a carbon nucleophile allowed access to trisubstituted 1,4-oxazepane derivatives (13EJO2076). 

The intramolecular reductive aldol reaction of keto-enones was successfully conducted under conditions similar to those described above, employing a cationic Rh complex and PI13P (Scheme 20) [34]. The keto-enone 63 was cyclized in the presence of added K2CO3 to give the ketone-aldol 64 in 72% yield with exclusive ds-selectivity. Dione-enone derivatives, for example 68 and 70, were efficiently cyclized to furnish bicyclic aldol products 69 and 71, respectively, wherein three stereogenic centers of the bicyclic product form stereoselectivity through the intermediacy of a Rh-enolate. 

The intramolecular cyclopropanation of appropriate y,(5-unsaturated a-diazoketones following a stereoselective catalytic reduction of the cyclopropyl ketone group provides a useful approach in diterpenoid synthesis. Some examples of the use of the cyclopropanation-reductive cleavage approach in synthesis are shown in equations 67 and 68l0f103. 

Looking at all the reactions that took place for the formation of the complex C, the heterocycle A plays the role of a molecular glue, which is possible because it represents both a Lewis acid and a Lewis base. As a result of this dual role, A places the electrophile (the ketone) and the hydride donor (the BH3) in close proximity. In this way, the complex C makes possible a quasi-intramolecular reduction of the ketone. It takes place stereoselectively in such a way as the arrangement of the reaction partners in C suggests (Figure 10.26). As a bicyclic... 

J. L. Chiara, J. Marco-Contelles, N. Khira, P. Gallego, C. Destabel, and M. Bemabe, Intramolecular reductive coupling of carbonyl-tethered oxime ethers promoted by samarium diiodide A powerful method for the stereoselective synthesis of aminocyclopentitols, J. Org. Chem., 60 (1995) 6010-6011. 

A series of innovative investigations by Kiyooka and co-workers have introduced the use of tandem reaction processes that commence with a stereoselective aldol addition reaction and are followed by C=0 reduction [13]. A chiral oxazaboroli-dine complex prepared from BH3-THF and A-/ -toluenesulfonyl (L)-valine controls the absolute stereochemical outcome of the aldol reaction. In a subsequent reaction, the /i-alkoxyboronate effects intramolecular reduction of the ester to furnish the corresponding /i-hydroxy aldehyde. 

Diisopropylchlorosilane was used in the stereoselective reduction of /Miydroxyketones to 1,3-diols60. In this stepwise process the first step is the silylation of the hydroxyl group and then a Lewis acid catalyzed intramolecular reduction (hydrosilylation) of the carbonyl to form the dioxasilacycles 22, cleavage of which provides the diol (equation 52). 

Sodium triacetoxyborohydride can reduce aldehydes selectively in the presence of ketones. However, a- and -hydroxy-ketones are reduced with this reagent. The reduction occurs stereoselectively to give predominantly the anti diol product. The reagent tetramethylammonium triacetoxyborohydride Me4NBH(OAc>3 has shown excellent selectivity for this transformation (7.88). Exchange of one of the acetoxy groups for the alcohol is thought to proceed stereoselective intramolecular transfer of hydride. 

The products presented in scheme 5 show that it should be possible by subsequent introduction of amino groups through halogen or oxirane functionalities, to get an efficient entry into a series of polyhydroxylated piperidines (azasugars) [6,7,30] by intramolecular reductive amination. This class of compounds gained much interest recently because of its biological activity as potential glycosidase inhibitors [31-33]. In scheme 8 novel substitution patterns of polyhydroxy piperidines (boxed), which we synthesized stereoselectively by our own new procedures [34], are compared with known compounds derived from natural sources. 

---