Diastereoselectivity Selectride reductions

Stereoselective Carbonyl Reductions. L-selectride reduction of U-acyl-Y-lactones has been shown to furnish the syn-reduction products in good yield and high diastereoselection which may be hydrolysed to threo-diols. The stereochemistry appears to be largely independent of the size of the acyl group and is in accord with reduction following the Felkin-Ahn transition-state model (Scheme 2). ... 

Usually, a stoichiometric amount of metal hydride, such as a selectride reagent, is required for diastereoselective reduction of aliphatic ketones to secondary alcohols. Now the same purpose can be achieved by the Ru-catalysed diastereoselective... 

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. 

In the attack by sterically undemanding reducing agents, this stereoelectronic effect is fully effective (for a completely different but perfectly diastereoselective reduction of 4-fert-butylcyclohexanone to the equatorial alcohol, see Figure 14.46). However, in the attack of such a bulky hydride donor as L-Selectride the stereoelectronic effect is overcompensated by the opposing steric effect discussed above. 

The facial selectivity for the reduction of a-(fluoroalkyl)- 3-sulfinylenamine (88) with K-Selectride was controlled by the sulfoxide, and proceeded with high diastereoselectivity to yield product 89 (Scheme 23).57... 

Coupling of these two readily available precursors leads to bis-enone 413 elaborated to 414 by chemo- and stereoselective hydrogenation of the more strained, bicyclic alkene with PhSiH3 in the presence of catal)dic Mo(CO)6, and K-selectride diastereoselective reduction (O Scheme 81). 

The reduction of iV-diphenylphosphinyl imines of substituted cycloalkanones with lithium tri-sw-butylborohydride (L-Selectride) provides highly diastereoselective conversions to protected axial primary amines in 83-96% yield17. The reduction of cyclohexylidene diphenylphos-phinyl imines with sodium borohydride is less diastereoselective17. 

We decided to investigate this reduction further and probe the effect of solvent, temperature, and reducing agent on the diastereoselectivity. Remarkably, changing the solvent to THF reversed the sense of selectivity. More bulky L-selectride showed improved selectivity over that observed with sodium borohydride. Lowering the temperature and moving to more nonpolar solvents increased the selectivity to 10 1 (Table 5.1). 

As shown in section 2.1.1 and figure 15, (-t-)-muricatacin 19 has been synthesized in 4 steps and 48 % overall yield from a very inexpensive starting material, L-glutamic acid. The key steps of the synthesis are a nitrous deamination of an a-amino acid with retention of the configuration of the stereogenic centre, and a very diastereoselective reduction of a-butyrolactonic ketone 18 with L-Selectride . The use of D-glutamic acid allowed the preparation of (-)-muricatacin 19 as well. 

A similar synthetic route led to 73b starting from (7 )-methyl ester isopropylideneglycerate (77b). However, in this case non-chelation-con-trolled reduction with L-Selectride resulted in poor diastereoselectivity (<60 40). Replacement of the MMT protecting group by the less hindered ethoxy-ethyl (EE) restored high diastereoselectivity (90 10). 

Diastereoselective hydride addition is quite versatile, and it provides facile synthetic access to ( —)-pinidine (661), an alkaloid isolated from several species of Pinus, as well as its unnatural isomer (+ )-pinidine (660b). The unstable aldehyde 655, prepared in four steps from 624 [202], undergoes Grignard addition with 4-pentenylmagnesium bromide followed by Swem oxidation to afford ketone 656 in 90% yield for the two steps. Stereoselective hydride addition with L-Selectride provides the -yn-alcohol 657 (91 9), while zinc borohydride reduction provides almost exclusively the anri-alcohol 658 (>99 1) (Scheme 144). 

Reduction of (23) with L-selectride was found to be highly diastereoselective (Scheme 4.16, Table 4.4). 

Reduction of the cA/ro-inositol derivative (145), made from quebrachitol, with K-selectride in THF and HMPA gave a high preponderance of the (S)-diastereomer (146). Surprisingly, replacement of the HMPA with 18-crown-6 led to reversal of the diastereoselectivity with up to 92% d.e. of the (/ )-product.il ... 

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