Me/transition metal-catalysed approach was investigated [48,49]. Within this regard, the mixture of Ru complexes for instance Shvo’s PDE3 Modulator site catalyst (C) [50], the amino-Cp catalyst D [51], or [Ru(CO)2Cl(5C5Ph5)] [52], as well as the lipase novozym 435 has emerged as particularly helpful [53,54]. We tested Ru catalysts C and D under several different circumstances (Table four). Inside the absence of a Ru catalyst, a kinetic resolution happens and 26 andentry catalyst lowering agent (mol ) 1 two 3 4 17 (ten) 17 (20) 17 (20) 17 (20) H3B Me2 H3B HF H3B HF catechol boraneT dra-78 20 -50 -78no conversion complex mixture 1:1 3:aDeterminedfrom 1H NMR spectra with the crude reaction mixtures.With borane imethylsulfide complex as the reductant and ten mol of catalyst, no conversion was observed at -78 (Table 3, entry 1), whereas attempted reduction at ambient temperature (Table three, entry 2) resulted within the formation of a complicated mixture, presumably as a result of competing hydroboration with the alkenes. With borane HF at -50 the reduction proceeded to completion, but gave a 1:1 mixture of diastereomers (Table three, entry three). With catechol borane at -78 conversion was once again total, however the diastereoselectivity was far from being synthetically useful (Table three, entry 4). On account of these rather discouraging benefits we did not pursue enantioselective reduction solutions further to establish the essential 9R-configuration, but regarded a resolution approach. Ketone 14 was first lowered with NaBH4 to the expected diastereomeric mixture of alcohols 18, which had been then subjected to the conditionsBeilstein J. Org. Chem. 2013, 9, 2544555.Scheme four: Synthesis of a substrate 19 for “late stage” resolution.Scheme five: Synthesis of substrate 21 for “early stage” resolution.Beilstein J. Org. Chem. 2013, 9, 2544555.Table 4: Optimization of situations for Ru ipase-catalysed DKR of 21.entry conditionsa 1d 2d 3d 4d 5d 6d 7e 8faiPPA:26 49 17 30 50 50 67 76 80(2S)-21b,c 13c 44 n. d. n. d. 38 n. i. 31 20 n. i. n. d. 65 30 n. d. n. d. n. d. n. d. n. d.Novozym 435, iPPA (1.0 equiv), toluene, 20 , 24 h C (2 mol ), Novozym 435, iPPA (ten.0 equiv), toluene, 70 , 72 h C (1 mol ), Novozym 435, iPPA (ten.0 equiv), Na2CO3 (1.0 equiv), toluene, 70 , 24 h D (two mol ), Novozym 435, iPPA (1.5 equiv), Na2CO3 (1.0 equiv); NPY Y2 receptor Activator Accession t-BuOK (five mol ), toluene, 20 , 7 d D (two mol ); Novozym 435, iPPA (1.five equiv), t-BuOK (five mol ), toluene, 20 , 7 d D (2 mol ), Novozym 435, iPPA (three.0 equiv), Na2CO3 (1.0 equiv), t-BuOK (3 mol ), toluene, 30 , 7 d D (five mol ), Novozym 435, iPPA (1.five equiv), Na2CO3 (1.0 equiv), t-BuOK (6 mol ), toluene, 30 , five d D (five mol ), Novozym 435, iPPA (3.0 equiv), Na2CO3 (1.0 equiv), t-BuOK (six mol ), toluene, 30 , 14 disopropenyl acetate; bn. d.: not determined; cn. i.: not isolated; ddr’s of 26 and (2S)-21 19:1; edr of 26 = six:1; fdr of 26 = 3:1.the resolved alcohol (2S)-21 were isolated in related yields (Table 4, entry 1). Upon addition of Shvo’s catalyst C, only minor amounts on the preferred acetate 26 and no resolved alcohol were obtained. Instead, the dehydrogenation item 13 was the predominant product (Table 4, entry two). Addition in the base Na2CO3 led only to a smaller improvement (Table 4, entry three). Ketone formation has previously been described in attempted DKR’s of secondary alcohols when catalyst C was used in mixture with isopropenyl or vinyl acetate as acylating agents [54]. For this reason, the aminocyclopentadienyl u complicated D was evaluated next. Very comparable outcomes were obta.
