Asymmetric Synthesis of (1-Ferrocenylalkyl)amine and 1,1′-Bis(1-aminoalkyl)ferrocene Derivatives

Abstract

The aldehydes 1 and 5 were converted to the corresponding SAMP hydrazones 2 and 6, respectively. Subsequent nucleophilic 1,2‐addition of organolithium reagents to the C−N double bonds and cleavage of the N−N hydrazine bond using an excess of BH3·THF afforded (1‐ferrocenylalkyl)amines (N‐protection → 4) and 1,1′‐bis(1‐aminoalkyl)ferrocenes (N‐protection → 8) in good overall yields (32−88%), with very high enantiomeric excesses (ee = 90−98%) and dl/meso ratios of up to 95:5.

Competition between planar and central chiral control elements in nucleophilic addition to ferrocenyl imine derivatives

“…In the absence of the element of planar chirality, the SAMP-hydrazone of ferrocenecarbaldehyde undergoes addition of n-butyllithium in 498% de, with the new centre having the (R)-configuration. 8,9 However, in the present case, the SAMP hydrazone 12 results in poor stereocontrol (dr = 2.1 : 1 determined on the crude thiourea product), although the major isomer of the thiourea 14, formed by addition of n-butyllithium and, without purification of the intermediate hydrazine 13, cleavage of the N-N bond and reaction with 4-nitrophenyl isothiocyanate, has the (R)-configuration, implying that the hydrazone auxiliary performs somewhat better than the oximebased auxiliary in controlling addition to the CQN bond. Again, the absolute configuration of the new stereocentre in thiourea 14 was established crystallographically (Fig.…”

“…[1][2][3][4][5][6] Most routes to such enantiopure a-ferrocenylalkylamines are either based on chiral ferrocenylalkanols, 7 or on nucleophilic addition to ferrocenyl imine derivatives, FcCHQNR (Scheme 1). For example, addition of organolithium reagents to Enders' SAMP-hydrazone 1 proceeds with excellent stereocontrol to give (R)-ferrocenylalkylamine derivatives in good yield, 8,9 whilst our own efforts in this field have centred on the use of chiral oxime ethers, 10 and addition of organolithium or Grignard reagents to the ferrocenyl oxime 2 in the presence of boron trifluoride etherate proceeds with excellent stereocontrol. 11,12 In these and other examples, [13][14][15][16] the auxiliary is readily cleaved to give the desired a-ferrocenylalkylamines.…”

“…With the failure to obtain both diastereoisomers of the desired ferrocenyl ureas using the ROPHy/SOPHy oxime ether methodology, we turned to the Enders RAMP/SAMP hydrazone protocol. These chiral auxiliaries normally provide excellent stereocontrol, not only in ferrocene derivatives, 8,9 but also in a range of other situations. 36 Therefore the SAMP and RAMP hydrazones 12 and 15 of (R p )-2-methylferrocenecarbaldehyde were prepared along with the hydrazone 17 derived from 1-aminopyrrolidine.…”

Ferrocenyl- and octamethylferrocenyl-substituted phenylenevinylene-, thienylenevinylene-, and 1,1′-ferrocenylenevinylene spaced ethynes: Synthesis, metathesis polymerization, and polymer properties

“…The convenience and versatility of the formylation-post-derivatization chemistry of unsubstituted [1][2][3][4][5][6][7][8][9], aminomethylated [10][11][12][13], and even polymethylated ferrocenes [14][15][16][17][18][19][20] predestinates such compounds as ideal candidates for the design of monomers. The respective polymer matrices bear chemically reversible electrophores and offer a wide application potential in materials science such as sensor technology [21,22], polyelectrolytes, ion exchangers, electron reservoirs, organic magnets and semiconductors, as well as photonic and NLO-active materials [22,23].…”

New Synthesis of Ferrocene Monocarboxylic Acid and Systematic Studies on the Preparation of Related Key-Intermediates

“…Less used older methods include: Sommelet reaction on amino ferrocenes, oxidation of ferrocenyl alcohols by manganese oxide, etc. More recently, the reaction between ferrocenyl lithium and triethyl orthoformate or DMF has been used, but these two or multistep procedures are more suitable for the preparation of the substituted ferrocenyl aldehydes or of the 1,1'-dialdehyde [47,48,72]. More recently, the reaction between ferrocenyl lithium and triethyl orthoformate or DMF has been used, but these two or multistep procedures are more suitable for the preparation of the substituted ferrocenyl aldehydes or of the 1,1'-dialdehyde [47,48,72].…”