Pd-Catalysed Hydrogenation

A-tosylimines were chosen since they can be easily prepared as pure E isomers and because of the electron-withdrawing character of the tosyl group, which reduces the basicity of the formed amines 38 and therefore their inhibition capacity by coordination to the catalytic species. 

---

Nitta, Y., Kubota, T., Okamoto, Y. (2000) Preparation of cinchonidine-modified Palladium catalysts for the enantioselective hydrogenation of ( )-fl// /ifl-Phenylcinnamic acid. Bull. Chem. Soc. Jpn., 73,2635-2641. Tungler, A., Nitta, Y., Fodor, K., Farkas, G., Mathe, T. (1999) Comparison of chiral modifiers in the Pd catalysed hydrogenation of phenylcinnamic acid and isophorone, J. Mol. Catal. A. Chem. 149, 135-MO. 

Selective catalytic hydrogenation of the 6,7-double bond of 17/3-acetoxy-7-methylandrosta-4,6-dien-3-one was achieved with Pd-C-PhCH20H and gave the 7/8-methyl dihydro-compound. Added FeCls has been reported to improve the selectivity of reduction of a,/S-enones in metal-ammonia reactions, thereby improving the yield of the saturated ketones. Similar improvements were observed in the lithium-ethylamine reductions at -78 C when a substantial excess of lithium was used and t-butyl alcohol was the proton source. The influence of solvent and added nitrogenous bases on the stereoselectivity of hydrogenation of A - and A -3-oxo-steroids with Pd catalysts has been studied, and the stereoselectivity of Pd-catalysed hydrogenation of various A -7-oxo-steroids has been reported to be unaffected by substituents at C-3 or C-17. 

As expected, Pd catalysed hydrogenation of the C3-C4 double bond of lactone 16.15 (Scheme 7) afforded the dihydroderivative 16.17 in which the C-3 methyl group was trans to H-2 (94). Comparison of the NMR data of compound 16.5, readily prepared from 16.17, with those of natural lactone 16.6 (Scheme 6) definitely proved the stereostructure of the latter sesquiterpene (94). Compound 16.6 was also synthesized from 5-lactaranolide 11.28 according to the reaction sequence shown in Scheme 6, which is a nice example of a general strategy for moving the carbonyl group of lactaranolides from C-5 to C-13 (94). 

Monflier et al. (1997) have suggested Pd catalysed hydrocarboxylation of higher alpha olefins in which chemically modified P-cyclodextrin (especially dimethyl P-cyclodextrin) is u.sed in water in preference to a co-solvent like methanol, acetone, acetic acid, acetonitrile, etc. Here, quantitative recycling of the aqueous phase is possible due to easy phase separation without emulsions. A similar strategy has been adopted by Monflier et al. (1998) for biphasic hydrogenations for water-in.soluble aldehydes like undecenal using a water-soluble Ru/triphenylphosphine trisulphonate complex with a. suitably modified p-cyclodextrin. 

Similarly, reactions which are substantially enhanced by the use of PTC can be carried out even with reduced use of PTC with substantial enhanced rates of reaction as has been demonstrated by Sivakumar and Pandit (2000) in the case of conversion of benzamide to benzonitrile. In the case of A-alkylation of diphenylamine with benzyl bromide, in the presence of KOH as the anion source and PEG methyl ether as the PTC, some improvement in the rate has been observed. (Cains et al., 1998). Metal catalysed hydrogenations, such as those based on Ni, Pd/C, and Ru/C also benefit from ultra-sound. 

Intramolecular version can be extended to polycyclization as a one-pot reaction. In the so-called Pd-catalysed domino carbopalladation of trienediyne 178, the first step is the oxidative addition to alkenyl iodide. Then the intramolecular alkyne insertion generates 179. One alkyne and two alkene insertions are followed. The last step is the elimination of /f-hydrogen. In this way, the steroid skeleton 180 is constructed from the linear trienediyne 178 [78]. 

The phenolic OH group can be removed by Pd-catalysed hydrogenolysis of its triflate 522 with triethylammonium formate [261]. Naphthol can be converted to naphthalene by the hydrogenolysis of its triflate. The Ni-catalysed reduction of aryl mesylates 523 is possible using MeOH and Zn as the hydrogen donor [262]. Smooth removal of phenol groups as triflates and mesylates is not possible by any other means. 

As mentioned in Scheme 7.3, although thermal ene reaction of the 1,6-enyne 320 gives only 1,4-dienes 324, the 1,3-diene 325 is formed by the Pd-catalysed reaction. No thermal ene reaction is possible with 342, but the smooth Pd-catalysed cyclization affords the 1,3-diene system 343, which has a skeleton analogous to 325 in Scheme 7.3. Notably, the reaction proceeds with migration of vinylic hydrogen. The 1,3-diene system formed by the cyclization is useful for further modification, typically Diels-Alder reaction. The 1,3-diene 343 formed from 342 is converted to sterepolide (344) by Diels-Alder reaction [140]... 

The commonest example of. v>w-addition is the heterogeneously catalysed hydrogenation of an alkene, using either Ni, Pt or Pd, or in the case of the reduction from an alkyne to an alkene, using the Lindlar catalyst. The reduction of an alkene can also be achieved using diimide. 

Now the alkene must be moved yet one more time around the ring to prepare the way for another intramolecular Heck reaction. Hydroboration (chapter 17) of 153 is regioselective because of the large N-Boc group and Swem oxidation completes the insertion of the ketone 155. Reduction and elimination use another palladium-catalysed reaction. Conversion to the triflate 157 is followed by Pd-catalysed transfer hydrogenation, the H atom coming from formic acid HC02H. 

Alkylidenecyclopropyl ketones 2, accessible by the Rh-catalysed cyclopropanation of allenes with a-diazo ketones, afford 4//-pyrans through a Pd-catalysed cycloisomerisation. In one instance, where the substrate lacked a hydrogen atom on the alkylidene moiety, a 2//-pyran was obtained <04JA9645>. 

Recently, an interesting principle of formation for 2-substituted quinoline derivatives was realized in the Pd-catalysed transfer hydrogenation/heterocyclization of (o-aminophenyl)ynones 60 in the presence of tertiary amin/formic acid to give 61 [96] ... 

Substituted chromans are formed from chroman-3-one through the Pd-catalysed coupling of its triflate with trialkyltin and boronic acid derivatives and subsequent hydrogenation <97TL5501>. 

---