The review examines the chiral amine literature from 2000-2009 (May) concerning enantioselective and diastereoselective methods for N-acylenamide and enamine reduction, reductive amination, and imine reduction. The reaction steps for each strategy, from ketone to primary chiral amine, are clearly defined, with best methods and yields for starting material preparation and final deprotection noted. Categories of chiral amines have been defined in Section 1 to allow the reader to quickly understand whether their specific target amine falls within a difficult to synthesize, or not, structural class. Amino acids are not considered in this work.

Chiral Amine Synthesis – Recent Developments and Trends for Enamide Reduction, Reductive Amination, and Imine Reduction

Although known for over 90 years, only in the past two decades has the chemistry of diboron(4) compounds been extensively explored. Many interesting structural features and reaction patterns have emerged, and more importantly, these compounds now feature prominently in both metal-catalyzed and metal-free methodologies for the formation of B–C bonds and other processes.

Diboron(4) Compounds: From Structural Curiosity to Synthetic Workhorse

CuH-Catalyzed Reactions

A novel zinc-catalyzed reduction of tertiary amides was developed. This system shows remarkable chemoselectivity and substrate scope tolerating ester, ether, nitro, cyano, azo, and keto substituents.

Zinc-Catalyzed Reduction of Amides: Unprecedented Selectivity and Functional Group Tolerance

The reduction of diverse functional groups is an essential protocol in organic chemistry. Transition-metal catalysis has been successfully applied to the reduction of olefins, alkynes, and many carbonyl compounds via hydrogenation or hydrosilylation; the latter presenting several advantages over hydrogenation. Notably, hydrosilylation generally occurs under mild reaction conditions, and consequently over-reduced products are rarely detected. Moreover, the great majority of hydrosilanes employed in this reaction are easily handled, inexpensive, or both. A large number of multiple bonds can be involved in this context, and the hydrosilylation reaction can be regarded as a useful method for the synthesis of silicon-containing organic molecules or a convenient way of reducing organic compounds. Furthermore, the silyl group can also be retained as a protecting group, a strategy that can be of great usefulness in organic synthesis. Since the first Wilkinson's catalyst-mediated hydrosilylation of ketones in 1972, metals such as rhodium and iridium have attracted most of the attention in this area. A wide array of catalytic systems for hydrosilylation reactions is nowadays available, which has allowed for a great expansion of the synthetic scope of this transformation. After having been overlooked in the early years, group 11 metals (Cu, Ag, and Au), especially copper, have emerged as appealing alternatives for hydrosilylation. The use of a stabilized form of copper hydride, the hexameric [(Ph3P)CuH]6, by Stryker represented a breakthrough in copper-catalyzed reduction reactions. Nowadays, several copper-based catalytic systems compare well with a variety of reported rhodium-based catalysts, which generally suffer from the high cost of the catalyst. Tertiary phosphine ligands are the most widely used in these transformations. However, other families such as N-heterocyclic carbenes (NHCs) have shown promising activities. Compared with copper, little attention has been paid to silver- or gold-based catalysts. Silver salts have been considered inert towards hydrosilylation, and they are often employed as innocent anion exchange reagents for the in situ generation of cationic transition metal catalysts. Despite the rare reports available, they have already shown interesting reactivity profiles, for example, in the chemoselective reduction of aldehydes in the presence of ketones. Furthermore, 1,2-hydride delivery is favored over 1,4-reductions for alpha,beta-unsaturated carbonyl compounds, in contrast with most copper-based systems.

Copper, silver, and gold complexes in hydrosilylation reactions.

The highly enantioselective reduction of imines is achieved by employing chiral Zn/diamine catalysts. This new catalytic protocol offers attractive features such as use of a non-precious metal and an inexpensive silane, easy modification of chiral diamine ligands and provides ready access to chiral amines in good yields and with excellent enantioselectivities.

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Zinc‐Catalyzed Enantioselective Hydrosilylation of Imines

Highly efficient conjugate reduction of α,β-unsaturated nitriles catalyzed by copper/xanthene-type bisphosphine complexes

Zinc‐Catalyzed Enantioselective Hydrosilylation of Imines.

Zinc-Catalyzed Enantioselective Hydrosilylation of Imines

α,β-Unsaturated nitriles are chemoselectively reduced to the corresponding saturated nitriles in high yields using a copper-DPEphos or Xantphos complex as catalyst in the presence of polymethylhydrosiloxane (PMHS) as the stoichiometric reducing agent and t-butanol as additive.

Bu-Mahn Park

Papers

Zinc‐Catalyzed Enantioselective Hydrosilylation of Imines

Highly efficient conjugate reduction of α,β-unsaturated nitriles catalyzed by copper/xanthene-type bisphosphine complexes

Zinc‐Catalyzed Enantioselective Hydrosilylation of Imines.

Zinc-Catalyzed Enantioselective Hydrosilylation of Imines

Highly Efficient Conjugate Reduction of α,β-Unsaturated Nitriles Catalyzed by Copper/Xanthene-Type Bisphosphine Complexes.