Efficient Asymmetric Synthesis of Silanediol Precursors from 1,5-Dihydrosiloles

Abstract

Dihydrosiloles are easily prepared from 1,3-dienes and dichlorosilanes, even on kilogram scale. Asymmetric hydroboration of a 3-alkyl-1,5-dihydrosilole, prepared from a 2-alkyl-1,3-diene, followed by treatment with aqueous HF results in Peterson fragmentation, forming optically active 3-alkyl-4-fluorosilyl-1-butenes. The fluorosilanes are stable to moisture but very reactive toward nucleophiles. In addition, they can be converted to nucleophilic silyllithium reagents.

Serine Protease Inhibition by a Silanediol Peptidomimetic

“…We have recently reported an asymmetric method for constructing the P 1 ′ methyl stereogenic center and we employed this chemistry to prepare 2 (Scheme 2). 23 Magnesium-mediated cycloaddition of isoprene with dichlorodiphenylsilane can be performed on >100 g scale. 24 Hydroboration of 5 with monoisopinocampheylborane at −20 °C leads to silacyclopentane 6 in 93% ee.…”

Bioactive Amino Acids, Peptides and Peptidomimetics Containing Silicon

“…This distillable product was found to undergo asymmetric hydroboration with Brown's isopinocamphylborane to give alcohol 81 in high ee. This alcohol, when treated with aqueous HF in ethanol at reflux, undergoes a near quantitative Peterson fragmentation to give fluorosilane 83 with stereochemistry of the methyl group set [70]. The fluoride in 83 undergoes high yield displacement with a broad range of nucleophiles, including sensitive chloromethyllithium to give 84 Oxidative cleavage of the alkene forms the desired α-methyl-β-silyl propionic acid (see Fig.…”

“…These fluorosilanes react readily with nucleophiles and can also be converted into nucleophilic silyllithium reagents [70]. An even more efficient conversion of 94 to protease inhibitor structures is described in Fig.…”

Synthetic methods : Part (iii) Heteroatom chemistry

“…78 The synthesis of dihydrosiloles from a magnesium-mediated reaction of 1,3-dienes with dichlorosilanes, at up to kilogram scale, was achieved by Sieburth's group. 79 The dihydrosiloles proved useful precursors to silane-based protease inhibitors. Siloles have also been studied by Xu and co-workers, who carried out the synthesis of bis-silicon bridged p-terphenyls 46.…”