A new chiral catalyst for the highly enantioselective addition of dialkylzinc reagents to aliphatic aldehydes

Abstract

Even purely aliphatic aldehydes, as well as aromatic aldehydes, were alkylated enantioselectively with dialkylzinc reagents in high enantiomeric excess using (1) as a chiral catalyst.Generally, enantioselective addition of organometallic reagents to aliphatic aldehydes is less enantioselective than addition to aromatic aldehydes,l probably owing to the stereoelectronic effect of the aryl groups.2There have been some recent reports on the enantioselective addition of dialkylzinc reagents to aldehydes using chiral catalysts.3 However, the maximum enantiomeric excess (e.e.

Straightforward synthesis of [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl]methanol and [(2S,4R)-1-cyclohexyl-4-methylpiperidin-2-yl](diphenyl)methanol: novel chiral ligands for the catalytic addition of diethylzinc to benzaldehyde to give rise to an extensive turn in the sense of asymmetric induction

“…The organic phase was washed with 1 M NaOH and then with brine, dried over anhydrous MgSO 4 , filtered and concentred under reduced pressure to obtain 63 mg of pure product (À)-5a (70% yield). White solid; mp 151-153°C; [a] D = À27.8 (c 0.6, CHCl 3 ); IR (ATR) 3256, 2932, 1452, 1101 cm À1 ; 1 H NMR (300 MHz, CDCl 3 ) d 0.95 (d. 3H, 3 J = 6.3 Hz, CH 3 ), 1.03-1.14 (m, 1H, cyclohexyl), 1.16-1.55 (m, 6H, NCH 2 CH 2 , CHCH 3 , cyclohexyl), 1.56-1.70 (m, 4H, NCH 2 CH 2 , NCHCH 2 , cyclohexyl), 1.79-1.86 (m, 2H, cyclohexyl), 1.94 (d, 1H, 2 J = 11.4 Hz, cyclohexyl), 2.39 (td, 1H, 2 J = 11.8 Hz, 3 J = 2.6 Hz, NCH 2 ), 2.78 (dc, 1H, 3 J = 11.4, 3.2 Hz, NCHCH 2 O), 3.14 (dt, 1H, 2 J = 11.8 Hz, 3 …”

“…Found: C,82.67;H,9.18;N,3.86 .8, 23.8, 26.3, 26.4, 26.5, 29.6, 29.9 (CHCH 2 CH 2 CH 2 , Cyclohexyl), 47.0 (NCH 2 ), 67. 3,65.4 (NCH,COCH), 173.8 (C@O). Anal.…”

“…2,25.4,26.0,26.5 (cyclohexyl,CH 2 ), 30.4 (CH 3 CH), 32. 3,33.8,37.3 (cyclohexyl,CH 2 ),44.5 (NCH 2 ),57.5,61.9 (CH),77.3 (CO),124.4,125.6,125.8,126.5,127.7,128.1 (ArCH),147.0,150.4 (ArC). Anal.…”

“…1 Chiral ligands for asymmetric catalysis have been generally derived from a small number of readily available natural products. [2][3][4][5][6][7] In order to obtain the two enantiomeric products it is necessary to have the two enantiomeric ligands but, in many cases, this is not possible because only one of them is available. Moreover, modulation of the catalytic properties through structural modifications in origin could be limited by the nature of precursors.…”

Total synthesis of (–)-spinosyn A

“…Oxidation of 21 with SO 3 ⅐pyridine gave the corresponding aldehyde in 91% yield (34). Treatment of this aldehyde with diethylzinc in the presence of (Ϫ)-N,Ndibutylnorephedrine then gave the C(21) alcohol 22 as a 9:1 mixture of diastereomers in 94% yield (35)(36)(37). Protection of alcohol 22 as the triethylsilyl ether proceeded in 94% yield.…”