Reduction of Aryl Ketones

FIGURE 13.36 Clemmensen reduction of aryl aldehydes and ketones. 

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Other S/N ligands have been investigated in the enantioselective catalytic reduction of ketones with borane. Thus, Mehler and Martens have reported the synthesis of sulfur-containing ligands based on the L-methionine skeleton and their subsequent application as new chiral catalysts for the borane reduction of ketones." The in situ formed chiral oxazaborolidine catalyst has been used in the reduction of aryl ketones, providing the corresponding alcohols in nearly quantitative yields and high enantioselectivities of up to 99% ee, as shown in Scheme 10.60. 

The reactions proceed with an e.e. of about 80% when the enantiopure ligand is used. Similar conditions using poly[oxy(methylsilylene)] (PMHS) as the hydride donor lead to reduction of aryl ketones with up to 98% e.e.188... 

The reduction of aryl ketones by Ni-Al alloy in water under reflux proceeded to give the methylene compounds within 2 h in 89.0-99.8% relative yields (Eq. 8.18).42... 

The PMHS/TBAF system provides both an excellent and practical approach to the reduction of aryl ketones to the benzyl alcohols.278 Similarly, the PMHS/ Triton B combination gives high yields of the benzyl alcohols.278... 

Yu J-Q, Wu H-C, Ramarao C, Spencer JB, Ley SV 2003) Transfer hydrogenation using recyclable polyurea-encapsulated palladium efficient and chemoselective reduction of aryl ketones. J Chem Soc Chem Commun 678-679... 

In situ production of phosphine-free CuH from CuCl or CuOAc (0.3-1.0 equivalents), in the presence of an excess of PhMe2SiH in DM I at room temperature, displays a remarkable preference for reductions of aryl ketones (e.g., 15) over aliphatic ones such as 16 (Eq. 5.23) [46]. Reactions require a day or more to reach completion, concentrations of 0.5 M notwithstanding, but yields have been uniformly good (77-88%) for the few cases examined. Aldehydes, however, show no such selectivity and are reduced to the corresponding primary alcohols, albeit in high yields. 

Substrate substituent effects on activity and enantioselectivity have been investi- gated in the enzymatic reduction of aryl ketones, using 24 recombinant ketoreduc-tases.308... 

The next quantum leap in catalysis after DuPhos has been the development of the ruthe-nium-diamine-bisphosphine catalysts (JST). This combination of ligands on ruthenium produces a highly active and enantioselective catalyst for the reduction of aryl ketones at mild conditions. Although this technology is relatively young, the potential is strong for many industrial processes that use this catalyst system. 

Asymmetric reduction of a-halo ketones An a-halo substituent increases the rate and enantioselectivity of reduction of aryl ketones by neat 1. Chemical yields of chloro-and bromohydrins thus obtained are usually >90% optical yields are usually also >90%. Chemical yields in reduction of a-iodo ketones are lower because of deiodination. The absolute configuration is (R) when 1 is derived from ( + )-a-pinene. As expected, optical yields are lower when the reduction is conducted with aliphatic a-halo ketones. 

Promise is held in MPV reactions carried out under catalytic conditions. Instead of, for example, stoichiometric amounts of aluminum as the metal ion activator, catalytic quantities of complexes of rhodium and iridium can sometimes be used to bring about the same reactions. Although the catalytic mechanisms have not been established, postulation of the usual six-membered transition state in the critical step of hydride transfer appears reasonable. The strongly basic conditions of the MPV reaction are avoided. Reductions of aryl ketones (69 equation 30) using (excess) isopropyl alcohol as hydrogen donor and at partial conversions have led to the formation of alcohol (70) in modest enantiomeric excesses with various chiral ligands. " ... 

Reduction of aryl ketones using PhaSnH and acetyl chloride has been reported. The stepwise process is indicated in Scheme 18. Depending on the nature of the carbonyl carbon, chloride and/or acetate intermediates are formed, of which the latter is trapped, but the former is further reduced by the tin hydride. 

As an application of selenium chemistry, reduction of aryl ketones with CO and H2O in the presences of selenium and DBU has been carried out. The reduction, indicated in Scheme 19, can be considered as a redox reaction by CO and H2O. This reaction proceeds in high yield with only a catalytic amount of selenium. Although the reaction mechanism has not been clarified, this reaction probably involves an or-ganoselenium hydride intermediate (60), which is known to give the corresponding hydrocarbon under the reaction conditions." ... 

Reduction of organic substrates to dianions can be divided into (a) reductions of polycyclic aromatics, (b) reductions of aryl-substituted alkenes or alkynes, (c) reductions of 4n 7i-electron systems, and (d) reduction of aryl ketones and derivatives. 

Other aminophosphines have also been sought and applied in different enantio-selective transformations, e. g., allylic substitution [56] (up to 95 % ee), and Ir-based imine hydrogenation (88% ee) [57]. Chiral aminophosphines have also been investigated in the asymmetric transfer hydrogenation of ketones (up to 84 % ee for the reduction of aryl ketones) [58],... 

The asymmetric reduction of aryl ketone can be achieved with ruthenium catalysts (Scheme 24), prepared separately or in situ by formation of [RuCl2(arene)]2 and ligand, in z-PrOH [81]. The high enantioselectivities and rate are very dependent upon the functionality of the substrate, T -arene and A -substitution of the diamino or amino alcohol ligands on ruthenium [81]. The hydrogen transfer reaction in z-PrOH is reversible, necessitating low concentrations, while extensive... 

In 2002 the Nguyen lab demonstrated that Al(0/-Pr)((7 )-BINOL) was an effective catalyst for the asymmetric reduction of aryl ketones (20).20 This methodology was recently extended to include the enantioselective reduction of imines (22) to the corresponding amine (23). ... 

The same HCOOH-EtjN system as hydrogen source, in conjunction with Ru(II) catalyst "8. is also quite superior to 2-propanol for the asymmetric reduction of aryl ketones.It allows for a much higher substrate concentration (2-10 M vs. < 0.1 M in 2-propanol). 

Styrenes. A modified Clemmensen reduction of aryl ketones using Zn(Hg) and some ethanol in refluxing formic acid gives styrenes ( -form major 5 examples, 69-83%). 

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