An efficient method for synthesising unsymmetrical silaketals: substrates for ring-closing, including macrocycle-closing, metathesis

Abstract

Diisopropylsilyl ethers were activated with N-bromosuccinimide, and reacted with a fluorous-tagged alcohol, to yield tethered substrates for ring-closing metathesis reactions.

Temporary Silicon‐Tethered Ring‐Closing Metathesis: Recent Advances in Methodology Development and Natural Product Synthesis

“…Several elegant approaches have been reported to circumvent these shortcomings. [19,20,21] Disubstituted alkenes: Mioskowski and co-workers reported a comparative study in the preparation of various heterocycles through the ring-closing metathesis employing Schrocks alkoxy imidomolybdenum, Grubbs first-and second-generation catalysts. [22] This study highlights the further advances in the scope of RCM reaction, focusing on the synthesis of various heterocycles.…”

Synthesis of Natural‐Product‐Like Molecules with Over Eighty Distinct Scaffolds

“…The metathesis substrates were each treated with a metathesis catalyst in refluxing dichloromethane (see Scheme for selected examples, and Supporting Information). In general, G I (Scheme ) was used with substrates in which one or both of the building blocks had been attached using a silaketal tether;14 with other substrates, the fluorous‐tagged catalyst15 f‐ HG II was usually used. The reactions were monitored, and additional catalyst was added as required.…”

“…The diversity of organic compounds has often been analysed in a chemically intuitive manner in terms of the ring systems in structures 2. 14, 18 We have assessed the skeletal diversity of our library in terms of an hierarchical approach that formalises the relationship between molecular scaffolds (Figure 1). 17 In this approach, terminal side chains are pruned to give a scaffold which is defined by the rings and unsaturated groups that rigidify the molecule.…”

Dichlorodiisopropylsilane

“…The first alcohol coupling can be done with the reagent chlorodiisopropylsilane and the resulting alkoxydiisopropylsilane oxidized with NBS to the alkoxybromodiisopropylsilane, which can then be coupled to a second alcohol with displacement of bromide to yield the unsymmetrical silaketal. 48, 49 Much larger cyclic systems containing the diisopropylsilyl group have been obtained by alkyne metathesis. The example shown in eq 18 describes the formation of a molecular triangle (not shown) and the rhomboid 33 involving the reactions between i-Pr 2 SiCl 2 and oxygen nucleophiles to form silyl diether 32, alkynylation of 32, and subsequent Mo(CO) 6 -catalyzed alkyne metathesis.…”