Hydrosilyation

Mechanism + Description

A number of silane reagents (RXSiHY and RXOZSiHY) will reduce amides to amines in the presence of metal catalysts. Typically these reactions proceed through the intimacy of O-silyl hemiaminals. Depending on the catalyst/silane, can get good functional group compatibility.

A related transformation, but mechanistically distinct, is the reduction of primary carboxamides which go via dehydration to the nitrile followed by reduction.

General comments

Amides can be reduced with SiH reagents in the presence of metal catalysts. Traditionally focused on PGM metals like Rh, Ru, Pt, Pd, Ir, Os, Re, base metals like Ti, Fe and Zn can also provide active catalysts. Tert amides are most reactive, but some catalysts will reduce secondary and primary amides. This does allow for some selectivity in molecules with multiple amide groups. A wide range of silanes have been reported for catalysed amide reduction –Et3SiH, (EtO)3SiH, PhSiH3, Me(EtO)2SiH, Polymethylhydrosiloxane (PMHS), Me2PhSiH and (Me2SiH)2O. Solvents are usually ethers or hydrocarbons.

Care needs to be exercised with alkoxysilanes as the hydride donor.

J . Am. Chem. Soc. 2010, 132, 1770–1771 Zinc-Catalyzed Reduction of Amides: Unprecedented Selectivity and Functional Group Tolerance  

In the presence of Lewis acids or metal catalysts, a metathesis  reaction  can occur to generate SiH4 which is highly flammable and explosive in  the presence of air.

Org. Process Res. Dev. 2010, 14 ,484–484 On the Perils of Unexpected Silane Generation

Key references

Doods and Cole Hamliton CATALYTIC REDUCTION OF AMIDES AVOIDING LiAlH4 OR B2H6 in Sustainable Catalysis: Challenges and Practices for the Pharmaceutical and Fine Chemical Industries, Wiley

Org. Synth. 200582, 188 CATALYTIC REDUCTION OF AMIDES TO AMINES WITH HYDROSILANES USING A TRIRUTHENIUM CARBONYL CLUSTER AS THE CATALYST

Tet. Lett. 2001, 42, 1945-1947 Transition-metal complex-catalyzed reduction of amides with hydrosilanes: a facile transformation of amides to amines

Topics in Catalysis 201053(15-18), 979-984 Selective Catalytic Reductions of Amides and Nitriles to Amines

Angew. chem. Int. Ed. 2009, 48, 9507-9510 A Convenient and General Iron-Catalyzed Reduction of Amides to Amines

Chem. Eur. J. 2011, 17, 12186-12192 Zinc-CatalyzedChemoselective Reduction of Tertiary and Secondary Amides to Amines

Tet. lett. 2011, 52, 4072-4075 Hydrosiloxane–Ti(OiPr)4: an efficient system for the reduction of primary amides into primary amines as their hydrochloride salts

Relevant scale up example

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