Lactols reduction

The stereoselectivity of this reaction rises when more bulky nucleophiles are employed (compare entries 7, 3,1, and 5). This is most impressively demonstrated by comparison of the y-lactol reduction with its allylation leading to 205 or 206, respectively (Scheme 10). Formation of tetrahydrofuran derivative 208, dihydrofuran 209, or unsaturated a-methylen-y-butyrolactone 207 illustrate that various modes of straightforward work-up procedures provide two different five membered heterocycles 93 b-96). A second example without the geminal dialkyl substitution at C-3 of the siloxy-cyclopropane depicted in Eq. 86 making available the annulated tetrahydrofuran-3-carboxylate 210 underlines the generality of the C-C-bond forming hydroxyalkylation reaction via ester enolates. 

Nucleophihc Additions to Sugar Lactones Followed by Lactol Reductions 7.2.9.1 Lewis Acid-Trialkylsilane Reductions... 

SCHEME 7.48 Lactol reduction with sodium cyanoborohydride. 

Compound (E) was prepared from levoglucosan and, after transformation into its tosylate and the corresponding epoxide, was opened with DMSO anion to give a dimethylated alcohol after desulfurization. The alcohol was then transformed into the corresponding lactol. Reduction of the lactol to the expected triol followed by a tandem protection-oxidation process afforded an aldehyde, which was then coupled with the vinyllithium reagent generated from the corresponding vinyl iodide [190]. The major diastereoisomer was transformed, after a... 

Scheme 2 Synthesis of lignan natural products from lactol reductions by Hong et al. [7]...

Evans synthesis of (-t)-phorboxazole B demonstrates the functional group tolerance of lactol reduction in a complex setting (Scheme 71) [129]. Selective deprotection of the triethylsilyl ether 270 provides the lactol 271, as a 92 8 mixture of closed/open forms that was carried on directly. Subsequent reduction of lactol 271 using the standard conditions afforded the bis-THP fragment 272 in good yield and high selectivity (96 %, dr = 95 5). 

Although the nature of the general polar effect suggested by Kamernitzsky and Akhrem " to account for axial attack in unhindered ketones is not clear, several groups have reported electrostatic interactions affect the course of borohydride reductions. Thus the keto acid (5a) is not reduced by boro-hydride but its ester (5b) is reduced rapidly further, the reduction of the ester (6b) takes place much more rapidly than that of the acid (6a). Spectroscopic data eliminate the possibility that in (5a) there is an interaction between the acid and ketone groups (e.g. formation of a lactol). The results have been attributed to a direct repulsion by the carboxylate ion as the borohydride ion approaches. " By contrast, House and co-workers observed no electrostatic effect on the stereochemistry of reduction of the keto acid (7). However, in this compound the acid group may occupy conformations in which it does not shield the ketone. Henbest reported that substituting chlorine... 

Conjugate addition of methyl magnesium iodide in the presence of cuprous chloride to the enone (91) leads to the la-methyl product mesterolone (92) Although this is the thermodynamically unfavored axially disposed product, no possibility for isomerization exists in this case, since the ketone is once removed from this center. In an interesting synthesis of an oxa steroid, the enone (91) is first oxidized with lead tetraacetate the carbon at the 2 position is lost, affording the acid aldehyde. Reduction of this intermediate, also shown in the lactol form, with sodium borohydride affords the steroid lactone oxandrolone... 

With the co side chain at C-12 in place, we are now in a position to address the elaboration of the side chain appended to C-8 and the completion of the syntheses. Treatment of lactone 19 with di-isobutylaluminum hydride (Dibal-H) accomplishes partial reduction of the C-6 lactone carbonyl and provides lactol 4. Wittig condensation8 of 4 with nonstabilized phosphorous ylide 5 proceeds smoothly and stereoselectively to give intermediate 20, the bistetra-hydropyranyl ether of ( )-1, in a yield of -80% from 18. The convergent coupling of compounds 4 and 5 is attended by the completely selective formation of the desired cis C5-C6 olefin. 

If it is assumed that the Mitsunobu glycosidation reaction described above proceeds through an SN2-type process with inversion of configuration at the anomeric position, then it follows that the desired / -glycoside can be formed selectively if pure a-lactol 17 is used in the reaction. Unfortunately, the /Mactol isomer of 17 is thermodynamically more stable than the a-diastereoisomer and is formed almost exclusively if the system is allowed to fully equilibrate. In the protic medium used for the Luche reduction, a signifi-... 

These reductions of lactols with Et3SiH 84b in combination of BE3 -OEt2, TfOH, or TMSOTf 20 have become standard reactions for synthesis of cyclic ethers [62-69]. Thus even co-hydroxyketones such as 1837 cyclize readily with excess EtsSiH 84b in the presence of TMSOTf 20, in high yields, via the lactols 1838, to give cyclic ethers such as the substituted oxepane 1839 in 90% yield [65] (Scheme 12.18). 

---