Pearlman’s catalysts

Lemiere and coworkers synthesized the antipicomavirus agent 3-0-Methylquercetin (76). A key transformation was the conversion of acetophenone 61a to 3-methoxyflavone 79. In the event, 61a and 3,4-dibenzyloxybenzoic anhydride (77) were allowed to react at 160 C in the presence of sodium carboxylate 78 to deliver the penultimate intermediate in 78% yield. Debenzylation of 79 in the presence of Pearlman s catalyst delivered the natural product in 99% yield. 

Catalytic hydrogenation of 5-oxy-7,8,9,10-tetrahydro-6a//-pyrido[l,2-a]quinoxalin-6-ylamines 352 over Pearlman s catalyst under 5 atm of H2 in MeOH for 5-7 days at room temperature gave 6,6u,7,8,9,10-hexahydro-5//-pyrido[ 1,2-u]quinoxalines (01EJOC987). 

Catalytic hydrogenation of 2-cyano-l-(2-nitrophenyl)piperidines over Pearlman s catalyst in a low-pressure hydrogenator under 1 atm of hydrogen in dioxane gave cyclic amidine A -oxides 352 (01EJOC987). 

Pearlman s catalyst provided the target compound 67 in 40% yield and 78% ee, completing the first asymmetric synthesis of this compound. 

Palladium catalysts, mostly palladium on carbon and Pearlman s catalyst, are used for the hydrogenolysis of the benzyl—nitrogen bond. However, in some cases, platinum, nickel, and copper chromite catalysts have also been used. 

JA754>, and -1,6-dione <2003EJ0268> over Pearlman s catalyst and other Pd-catalysts (PdCl2, or Pd/C) provided different (optically active) pipecolic acid derivatives. 

The hexahydro-l//-pyrrolo[2,l-f][l,4]oxazin-l-one 82 (obtained by radical cyclization see Section 11.11.7.3) was transformed into the proline derivative 83 by hydrogenation in the presence of the Pearlman s catalyst and a stoichiometric amount of trifluoroacetic acid (TFA) (Scheme 10). This reaction led with high yield to the disub-stituted proline 83 in an enantiomerically pure form <2003SL1058>. In an analogous approach, the chiral (4/ ,7/ ,8aA)-methyl 6,6-dimethyl-l-oxo-4-phenylhexahydro-l//-pyrrolo[2,l-r-][l,4]oxazine-7-carboxylate 84 was hydrogenated on Pd(OH)2 in the presence of TFA to give enantiomerically pure 5,5-dimethylproline derivatives 85 <2001SL1836> (Scheme 10). 

Deacetylation and catalytic hydrogenation with Pearlman s catalyst, in the absence of any asymmetric catalyst, afforded the serine conjugate 109 in a 6 1 ratio in favor of the desired (L)-isomer. 

The synthesis of the module is provided in Scheme 10.5 (Kushner et al. 2007). Double alkylation of ethyl acetoacetate followed by guanidine condensation afforded alkenyl-pyrimidone intermediate 24 (Kushner et al. 2007). Isocyanate 25 was coupled to pyrimidone 24 to yield 26. Upon dimerization in DCM, RCM effectively cyclized the two UPy units (Mohr et al. 1997 Week et al. 1999). A one-pot reduction and deprotection through hydrogenation using Pearlman s catalyst gave diol module 27. Finally, capping 27 with 2-isocyanatoethyl methacrylate at both ends provided the UPy sacrificial cross-linker 28, which was thoroughly characterized by H- and C-NMR, Fourier transform IR (FTIR), and mass spectrometry. 

Further elaboration of the sulfur cycloadducts could be achieved by the use of a Pummerer rearrangement in the syntheses of 5-(hydroxymethyl)prolines. Oxidation of adduct 298 to sulfoxide 299, followed by treatment with TEA in DCM and quenching with either methanol or benzyl alcohol, delivered the Pummerer products 300 in 57% yield for R = Me and 38% for R = Bn as single diastereoisomers. Raney Ni desulfurization and Pearlman s catalyst mediated hydrogenolysis, for R = Bn furnished the final enantiopure proline derivative (Scheme 3.99). 

Mori has independently developed a procedure for the cyclization/stannylsilylation of enynes similar to that developed by Lautens. As an example of Mori s procedure, reaction of dimethyl allylpropargylmalonate with trimethylsilyltributylstannane catalyzed by Pearlman s catalyst [Pd(OH)2/C] in THF at room temperature for 20 h formed cyclopentane 94 [X = C(C02Me)2] in 90% yield (Equation (61)). The transformation was compatible with a number of functional groups, tolerated limited substitution of the G=C bond, and was applicable to the synthesis of nitrogen heterocycles. In a notable example, reaction of the benzhydryl-protected allylpropargylamine 95 with MesSiSnBus catalyzed by Pd(OH)2/C formed the bis(functionalized) octahydroindole 96 in 66% yield as a single diastereomer (Equation (62)). 

Reductive amination of benzaldehyde with (R)-81 provided the corresponding benzyl amine, which was reductively alkylated with formaldehyde to give 82 (Scheme H) " Compound 82 was debenzylated by hydrogenation in the presence of Pearlman s catalyst to afford frovatriptan ((/J)-6). Alternatively, monomethylation of amine (/ )-81 was affected by treatment with carbon disulfide and dicyclohexylcarbodiimide in pyridine to provide isothiocyanate 83, which was reduced with sodium borohydride to give (l )-6. 

Optically active pipecolic acids, and their 2-substituted derivatives were prepared by the catalytic hydrogenation of the respective optically active 4-phenylperhydropyrido[2,l-c][l,4]oxazin-l-ones and their 9a-substituted derivatives over Pearlman s catalyst in good yields (05TA3858). 

---