Catalytic Enantioselective Hydrogenation of N-Alkoxycarbonyl Hydrazones: A Practical Synthesis of Chiral Hydrazines

Abstract

An enantioselective hydrogenation of hydrazones catalyzed by Rh complexes (Rh-Josiphos or Rh-Taniaphos) has been developed. The protocol can be applied to hydrazones with three different protective groups (Boc, Cbz, and methoxycarbonyl), allowing for selective deprotection and further elaboration of the hydrazine products in the presence of other functional groups.

Asymmetric Hydrogenation of Imines

“…For a similar type of hydrazine substrates, the recent application of electron-rich but ferrocene-based ligands such as Josiphos by Yoshikawa and Tan showed promising results (64-92% ee, Scheme 2) [17].…”

“…Rh-based chiral catalysts are the pioneers for these substrates [16,124], but examples of Pd-based chiral catalysts have recently become more dominant. The palladium catalysts of biaryl diphosphine ligands, such as BINAP analogues [114], as well as the highly electron-donating ligands, such as TangPhos [112] and ferrocene-based ligands [17], have shown extraordinary efficacies. Moreover, the removal of the different N-X protecting and activating group to obtain the primary amine is easy and can easily be scaled up (Scheme 41).…”

“…The N-N bond in N-aroylhydrazones can be readily cleaved by samarium diiodide (SmI 2 ) almost instantaneously at 20 C, and the deprotection proceeds with no loss of optical purity [16]. The selective deprotection of the N-Boc hydrazine product can be easily deprotected by treatment with benzenesulfonic acid at 60 C to give unprotected hydrazine without affecting enantio purity and the ester group [17]. Similarly, the acid-catalyzed removal of the phosphinyl group is also known to be easy [125].…”

Evaluation of 3,3′-Triazolyl Biisoquinoline N,N′-Dioxide Catalysts for Asymmetric Hydrosilylation of Hydrazones with Trichlorosilane

“…Since this initial breakthrough, many excellent transition metal-catalyzed methods for the asymmetric reduction of hydrazones have been developed. The majority of these examples utilized rhodium-based catalysts [3][4][5][6][7][8][9][10][11][12][13] but palladium- [14][15][16][17], iridium- [18], ruthenium- [19], nickel- [20][21][22][23] and cobalt- [24] based catalysts are also reported (Scheme 1, Equation ( 1)). While their reaction scopes are impressive, no metal-free 'green' counterpart (i.e., organocatalysis method) has been reported to the best of our knowledge, except for two scattered examples.…”

Metal-Catalyzed Asymmetric Hydrogenation of C═N Bonds

“…In order to access enantiopure protected hydrazines, Yoshikawa's and Tan's group developed a rhodium(I)-based catalytic system for the asymmetric hydrogenation of N-alkoxycarbonyl hydrazones (Scheme 80). 107 Among the studied diphosphines, Josiphos-type ligands L81 established itself as the most suitable in terms of selectivity and reactivity. By using low catalyst loading, the hydrazines were formed with total conversion and moderate to good enantioselectivity in methanol.…”