Synthesis of α-alkyl-α-aminosilanes by rhodium-catalyzed hydrosilylation of Boc-protected vinyl amines

Hewitt, G.; Somers, Joseph J.; Sieburth, Scott McN.

doi:10.1016/s0040-4039(00)01827-x

Cited by 18 publications

(4 citation statements)

References 8 publications

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“…This result is consistent with that of the hydrosilylation of 1A ( Table 1 , entry 7). 16 On the other hand, when PCy 3 ·HBF 4 was employed, the hydrosilylated products did not form. 12 Additionally, when we subjected allylamine 7A , which is another possible intermediate, under the same reaction conditions, 17 3Aa was obtained in 21% yield along with 41% yield of 4Aa .…”

Section: Resultsmentioning

confidence: 99%

Rh-catalyzed regiodivergent hydrosilylation of acyl aminocyclopropanes controlled by monophosphine ligands

2017

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Section: Resultsmentioning

confidence: 99%

Rh-catalyzed regiodivergent hydrosilylation of acyl aminocyclopropanes controlled by monophosphine ligands

2017

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“…Later, Murai and Kato claimed that the N -carbonyl group directed the hydrosilylation to the α-position of the enamide as depicted in Figure . On the other hand, Sieburth and co-workers’ investigation of this reaction between diphenylmethylsilane and Boc-substituted enamines provided only low yields of the silicon-containing product . It became therefore evident that an initial optimization study was required in order to obtain good yields of the hydrosilylated product as one regioisomer.…”

Section: Double Hydrosilylation: An Alternative Strategymentioning

confidence: 99%

Efficient Routes to Carbon–Silicon Bond Formation for the Synthesis of Silicon-Containing Peptides and Azasilaheterocycles

2012

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Silasubstitution, where silicon is substituted for carbon at specific sites of the substrate, has become a growing practice in medicinal chemistry. Introducing silicon into bioactive compounds provides slight physical and electronic alterations to the parent compound, which in certain instances could make the substrate a more viable candidate for a drug target. One application is in the field of protease inhibition. Various silane diol isosteres can act as potent inhibitors of aspartic and metalloproteases because of their ability to mimic the high-energy tetrahedral intermediate in peptide bond hydrolysis. In particular, since 1998, the Sieburth group has prepared a number of functionalized peptide silane diol isosteres. In a seminal study, they demonstrated that these molecules can bind to the active site of the enzymes. Inspired by these results, we initiated a study to develop a concise and straightforward route to access highly functionalized silicon diol based peptidomimetic analogs, which we describe in this Account. The synthesis of such analogs is challenging because the dipeptide mimics require the formation of two carbon-silicon bonds as well as two chiral carbon centers. Our first strategy was to assemble the two C-Si bonds from diphenylsilane through an initial regioselective hydrosilylation step of a terminal alkene, followed by lithiation of the formed alkyldiphenylsilane by a simple lithium metal reduction. Subsequent diastereoselective addition of this silyllithium species to a tert-butylsulfinimine provided a rapid method to assemble the dipeptide mimic with stereochemical control at the new chiral carbon center adjacent to the silicon. This strategy worked with a wide range of functional groups. However, there were some limitations with the more elaborate targets. In particular, we needed to exchange the phenyl groups of the diphenylsilane with aryl groups that were more labile under acidic conditions in order to introduce Si-O bonds in the end product. We demonstrated that a variety of Ar(2)SiH(2) compounds with methyl substituents on the aromatic core could effectively undergo hydrosilylation and reductive lithiation with a soluble reducing agent, lithium naphthalenide. The electron-rich aromatic groups were more acid labile and, depending on the conditions, could produce either the silane diol or the silanol. In an alternative strategy, we used a highly regioselective Rh-catalyzed sequential double hydrosilylation to form the two C-Si bonds with a single catalyst. This approach is a more efficient, atom economical way to synthesize a wider range of highly functionalized organosilanes with the added possibility of extending this method into an asymmetric protocol. By this method, various functional groups that were not previously tolerated in the lithiation protocol, including OBn, OAc, furyl, and thiophenes, could now be incorporated. Hydrosilylation of a terminal olefin and a peptide functionalized with an enamide at the C-terminus achieved the desired silane in high yields in a one pot r...

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“…In their paper, the substrate scope was moderate to high yielding but was limited to nonbulky silanes, dimethylphenylsilane, triethylsilane, and simple enamides, many lacking complexity at the β-position. Sieburth and co-workers surmised that N -alkenyl carbamates could also undergo hydrosilylation at the α-position with more bulky silanes (Scheme ) because Murai and Kato demonstrated that this reaction could also proceed with N -alkenyl ureas . Although this strategy would have provided a more expedient and straightforward synthesis of the desired compounds, the approach was not used since then due to the low reactivity of Rh 2 (OAc) 4 with diphenylmethylsilane and Boc-protected enamides.…”

Section: Introductionmentioning

confidence: 99%

Regioselective Rh(I)-Catalyzed Sequential Hydrosilylation toward the Assembly of Silicon-Based Peptidomimetic Analogues

Min

Skrydstrup

2012

J. Org. Chem.

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A highly regioselective Rh(I)-catalyzed hydrosilylation of enamides is presented. This mild protocol allows access to a wide variety of different arylsilanes with substitution at the β-position of the enamide and functionalization on the alkyl chain tethered to the silane. This protocol is extended to include a sequential one-pot hydrosilylation. Using diphenylsilane as the appendage point, hydrosilylation of a protected allyl alcohol followed by hydrosilylation of an enamide generates a complex organosilane in one step. This highly convergent strategy to synthesize these functionalized systems now provides a way for the rapid assembly of a diverse collection of silane-based peptidomimetic analogues.

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Synthesis of α-alkyl-α-aminosilanes by rhodium-catalyzed hydrosilylation of Boc-protected vinyl amines

Cited by 18 publications

References 8 publications

Rh-catalyzed regiodivergent hydrosilylation of acyl aminocyclopropanes controlled by monophosphine ligands

Rh-catalyzed regiodivergent hydrosilylation of acyl aminocyclopropanes controlled by monophosphine ligands

Efficient Routes to Carbon–Silicon Bond Formation for the Synthesis of Silicon-Containing Peptides and Azasilaheterocycles

Regioselective Rh(I)-Catalyzed Sequential Hydrosilylation toward the Assembly of Silicon-Based Peptidomimetic Analogues

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