Me/transition metal-catalysed approach was investigated [48,49]. In this regard, the mixture of Ru complexes like Shvo’s catalyst (C) [50], the amino-Cp catalyst D [51], or [Ru(CO)2Cl(5C5Ph5)] [52], along with the lipase novozym 435 has emerged as specifically helpful [53,54]. We tested Ru catalysts C and D beneath a number of situations (Table 4). Within the absence of a Ru catalyst, a kinetic resolution occurs and 26 andentry catalyst decreasing agent (mol ) 1 2 three 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 three:aDeterminedfrom 1H NMR spectra of your crude reaction mixtures.With borane P2Y12 Receptor Antagonist custom synthesis imethylsulfide complicated as the reductant and 10 mol of catalyst, no conversion was observed at -78 (Table 3, entry 1), whereas attempted reduction at ambient temperature (Table three, entry two) resulted in the formation of a complex mixture, presumably due to 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 3). With catechol borane at -78 conversion was once again complete, however the diastereoselectivity was far from getting synthetically helpful (Table three, entry four). On account of these rather discouraging final results we did not pursue enantioselective reduction techniques further to establish the expected 9R-configuration, but regarded as a resolution approach. Ketone 14 was very first decreased with NaBH4 P2Y6 Receptor Antagonist Storage & Stability towards the expected diastereomeric mixture of alcohols 18, which have been then subjected to the conditionsBeilstein J. Org. Chem. 2013, 9, 2544555.Scheme 4: 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 circumstances 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 (two mol ), Novozym 435, iPPA (10.0 equiv), toluene, 70 , 72 h C (1 mol ), Novozym 435, iPPA (10.0 equiv), Na2CO3 (1.0 equiv), toluene, 70 , 24 h D (two mol ), Novozym 435, iPPA (1.five equiv), Na2CO3 (1.0 equiv); t-BuOK (5 mol ), toluene, 20 , 7 d D (two mol ); Novozym 435, iPPA (1.5 equiv), t-BuOK (5 mol ), toluene, 20 , 7 d D (two mol ), Novozym 435, iPPA (3.0 equiv), Na2CO3 (1.0 equiv), t-BuOK (3 mol ), toluene, 30 , 7 d D (five mol ), Novozym 435, iPPA (1.5 equiv), Na2CO3 (1.0 equiv), t-BuOK (six mol ), toluene, 30 , 5 d D (5 mol ), Novozym 435, iPPA (three.0 equiv), Na2CO3 (1.0 equiv), t-BuOK (6 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 have been isolated in related yields (Table 4, entry 1). Upon addition of Shvo’s catalyst C, only minor amounts on the desired acetate 26 and no resolved alcohol have been obtained. Alternatively, the dehydrogenation product 13 was the predominant item (Table four, entry 2). Addition of your base Na2CO3 led only to a small improvement (Table four, entry 3). Ketone formation has previously been described in attempted DKR’s of secondary alcohols when catalyst C was made use of in combination with isopropenyl or vinyl acetate as acylating agents [54]. Because of this, the aminocyclopentadienyl u complex D was evaluated next. Extremely similar final results have been obta.
