Trisiamylborohydride, lithium

Reduction of cyclic ketones.l These complexes selectively reduce cyclic ketones to the less stable alcohol. The most stereoselective reagent is that in which the R group is /-butyl this complex is comparable to lithium trisiamylborohydride in stereoselectivity. 

Stereoselective reductions based on complexed borohydrides have also proved of value in many instances in particular they have been of use in the synthesis of epimeric cyclic alcohols. For example, the reduction of 4-t-butylcyclo-hexanone to the cis-alcohol [99.5%, arising from equatorial hydride ion attack (i)] is effected by L-Selectride (lithium tri-s-butylborohydride, cf. Section 4.2.49, p. 448), or LS-Selectride53 (lithium trisiamylborohydride, cf. Section 4.2.49, p. 448) but to the trans-alcohol [98%, arising from axial hydride ion attack (ii)] with lithium butylborohydride.54 The experimental details of these reductions are given in Expt 5.34. 

Diastereoselective reduction of acyclic a, -dialkoxy ketones.3 Reduction of the ketone 2 with this hydride results in the alcohol 3 with high syn-selectivity (97 3). The same syn-selectivity is observed with lithium trisiamylborohydride, but the yield is lower. The product was used for a synthesis of (+ )-4, a pheromone of a species of ants. 

Conjugate addition.s The key step in a stereocontrolled synthesis of the Lyth-raceae alkaloid lasubine II (4) is the conjugate addition of an alkylcopper complexed with BF3 to the N-acyl-2,3-dihydro-4-pyridone 1 to give the d.v-product 2 in 56% yield and >96% stereoselectivity. Hydrogenation in the presence of Li2C03 effects cyclization and deprotection of nitrogen to give the ketone 3, which is reduced stereoselectively by lithium trisiamylborohydride to the desired alcohol 4. 

Stereoselective reduction of ketones. This borohydride (1) is comparable to lithium tri-.ver-butylborohydride (4. 312-313) for stereoselective reduction of cyclic ketones to the less stable alcohols, but less stereoselective than lithium trisiamylborohydride (7, 216-217). The by-product formed in reductions with I can be removed as an insoluble ate complex formed by addition of water, simplifying isolation of the reduction product. 

Lithium trisiamylborohydride (LTSBH) shows unique stereoselectivity in the reduction of unhindered ketones.81 Ketones such as 4-t -butylcyclohexa-none undergo exclusive equatorial attack yielding the cis-carbinol. The reagent is superior to LTMBH and L-Selectride. 

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). 

Alkyl borohydrides with even greater steric hindrance but with similar reactivity and selectivity to the Selec-trides, were prepared from trisiamylborane (siamyl = Me2CH2CHMe- s tri-scc-isoamyl, sec. 5.2.A). Lithium trisiamylborohydride [LiBH(CHMeCHMe2)] and the potassium salt [KBH(CHMeCHMe2)], are similar to the L- and the K-Selectrides and are called LS-Selectride and KS-Selectride, respectively. in Bonjoch s synthesis of aeruginosin 298-A, LS-Selectride reduction of 157 gave 158 in 53% yield. 

Lithium trisiamylborohydride, prepared in quantitative yield from t-butyl-lithium and trisiamylborane, completely reduces moderately hindered ketones with high stereoselectivity. Norcamphor is reduced to the endo-alcohol of 99.5% isomeric purity however, camphor is relatively inert to the reagent at 0°C (2h), and only 10% conversion is achieved in 24 h. It is possible to achieve more complete conversion at a higher temperature, viz. 80% conversion into the exo-alcohol of 99.3 % isomeric purity in 72 h at 25 °C. 

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