Ketones, reaction with Selectride

Other cyclic or bicyclic ketones do not have a convex side but only a less concave and a more concave side. Thus, a hydride donor can add to such a carbonyl group only from a concave side. Because of the steric hindrance, this normally results in a decrease in the reactivity. However, the addition of this hydride donor is still less disfavored when it takes place from the less concave (i.e., the less hindered) side. As shown in Figure 10.10 (top) by means of the comparison of two reductions of norbomanone, this effect is more noticeable for a bulky hydride donor such as L-Selectride than for a small hydride donor such as NaBH4. As can be seen from Figure 10.10 (bottom), the additions of all hydride donors to the norbomanone derivative B (camphor) take place with the opposite diastereoselectivity. As indicated for each substrate, the common selectivity-determining factor remains the principle that the reaction with hydride takes place preferentially from the less hindered side of the molecule. 

The formed ketone is selectively reduced to an alcohol with lithium-tris-sec-butylborohydride (L-Selectride ) at -78 °C in only 30 min.. Only one diastereomer is built. Because lithium belongs to the non-chelating cations, the reaction proceeds through transition state 48 proposed by Felkin and Anh. 1 To remind In the most stable conformation the largest group of the stereogenic center is perpendicular to the carbonyl group. 

Of two ketonic C=0 double bonds, the sterically less hindered one reacts preferentially with a hydride donor the bulkier the hydride donor, the higher the selectivity. This makes L-Selectride the reagent of choice for reactions of this type (Figure 10.7, left). 

The starting material for the octahydronaphthopyranone core is 91 (O Scheme 11), which has been used in the total synthesis of herbimycin A (81). It was necessary to invert the C4-con-figuration for the crucial intramolecular Diels-Alder reaction at a later stage. Compound 91 was oxidized to ketone 104, which was stereoselectively reduced with L-Selectride to provide... 

The same two ketones featured again in a synthesis of ( )-lasubine II (910) by Pilli et al. (Scheme 119) (368,369). In this case, reaction of A -Boc-2-ethoxypiperidine (925) with enone 926 in the presence of trimethylsilyl triflate sparked off a remarkably efficient (90%) one-pot synthesis involving condensation (via an A -acyliminium ion to give the intermediate 927), deprotection, and intramolecular conjugate addition. The familiar products 921 and 922 were obtained as a 3 2 mixture. Base-induced epimerization of the mixture enriched the latter component, which was converted into ( )-910 by reduction with LS-Selectride (lithium trisiamylborohydride) according to the procedure developed by Comins (vide infra). 

Reactions on the three-carbon bridge of oxabicyclo [3.2.1] compounds have been reported but less systematically studied. Because the majority of these compounds are derived from oxyallyl cation cycloadditions, most experiments on the three-carbon bridge involve addition to the bicyclic ketone. The parent oxabicyclo[3.2.1] ketone 90 undergoes reduction with bulky hydride sources such as L-selectride to generate the endo alcohol, Eq. 68 [112]. Presumably, the selectivity is due to equatorial attack of the hydride at the ketone of the pyran-one in a pseudo chair conformation. The exo alcohol is prepared from the endo alcohol by a Mitsunobu inversion-hydrolysis sequence [113]. 

Exposing 645 to a similar reaction sequence results in ketone 651, which is reduced with L-Selectride almost exclusively to 652. Subsequent functional group transformations of 652 to trans-(2S,5S)-pyrro inQ 653 followed by Wacker oxidation and reductive deprotection with concommitent cyclization affords ( + )-indolizidine 195B (654) and its C-5 epimer (86 14). A comparison with the natural product established the absolute configuration of natural (-f )-654 to be 3S,5S,9S [204] (Scheme 143). 

In 2006, Enders and Vrettou [32] reported a concise total synthesis of (-l-)-poly-oxamic acid (82) through an organocatalytic Mannich reaction (Scheme 17.12). Asymmetric Mannich reaction of ketone 79 and Boc-protected imine 80 using L-proline 24 afforded the adduct 81 in 85% yield as a mixture of diastereomers with 92% ee (>98 2 dr). A stereoselective reduction of 81 using L-selectride, followed by ozonolysis and subsequent acid deprotection completed the total synthesis of (-l-)-polyoxamic acid (82). 

Vinyl sulphones are versatile intermediates for the synthesis of a variety of compounds (e.g.y see ref. 46). Julia et al. have developed a method whereby the a-sulphonyl ketones (176), which are produced by the reaction of the sulphone (175) with esters or with aldehydes followed by oxidation, are converted into ( )- or (Z)-vinyl sulphones, (178) or (179), completely stereospecifically. The a-sulphonyl ketones (176) are reduced with lithio Selectride to give the r/rreu-P-hydroxy-sulphone (177) as the only isomer. Elimination of the tosylate that may be derived from (177) gives the E)- my sulphone (178), whereas analogous elimination of the acetate that is derived from (177) furnishes the (Z)-vinyl sulphone (179). Hsiao and Shechter have prepared a-substituted vinyl... 

Stereoselective reduction of a-silyl ketones such as 182 with metal hydride reagents such as DIBAH, UAIH4, NaBH4, and L-Selectride has been reported to give the corresponding yS-hydroxyalkylsilanes 183 (Scheme 2.116) [11, 304, 316, 319]. Peterson reaction of the 2-silyl-l,3-diol 183 with KH gives a mixture of the corresponding alkene 184 and its isomer 185. 

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