Enantioselective synthesis via sparteine-induced asymmetric deprotonation

Abstract

Abstract

Efficient Desymmetrization ofmeso-cis-1,2-Cyclohexanedimethanol with Differentiation between Diastereotopic and Enantiotopic C−H Bonds by (−)-Sparteine-Mediated Deprotonation

“…As we have already reported, [7,8] the chiral base butyllithium/(À)-sparteine [9] has a pronounced tendency to discriminate in the rate of abstraction of enantiotopic protons in alkyl carbamates. The method has also been applied to N-Bocpyrrolidines, [10,11] several benzylic substrates, [12] ferrocenes, [13] P,P-dimethylarylphosphane derivatives, [14] as well as to the kinetic resolution of a racemic allyl carbamate [15] and of several b-stereogenic alkyl carbamates.…”

“…It can be concluded from these experiments that the kinetically controlled, substrateinduced deprotonation step favors the unlike-process [25] [RScheme 4. Deprotonation of cis-1,2-cyclohexanedimethyl dicarbamate (8) with sec-BuLi in the presence of (À)-sparteine or TMEDA and the subsequent reaction with electrophiles. Reaction conditions: a) 1) NaH, THF, 30 min, room temperature, 2) CbyCl, THF, reflux, 16 h. b) sec-BuLi/4 (2.2 equiv), toluene, À 78 8C, 4 h. c) sec-BuLi/TMEDA (2.2 equiv), toluene, À 78 8C, 4 h.…”

New C-substituted (1S,4S)-2,5-diazabicyclo[2.2.1]heptane derivatives. Preparation utilizing the directed metalation strategy. Application in enantioselective catalysis

“…for C 19 H 22 N 2 O: C,77.52;H,7.53;N,9.52. Found: C,77.52;H,7.65;N,9. 2, 29.7, 37.6, 39.7, 47.0, 62.4, 64.2, 65.8, 75.3, 76.6, 121.3, 123.8, 123.9, 124.0, 124.3, 124.4, 126.7, 128.4, 128.6, 130.1, 130.3, 130.5, 130.8, 131.0, 144.2, 145.4) 7,36.6,48.3,63.6,63.7,73.5,77.0,81.1,119.8,120.2,124.0,125.0,127.4,128.8,129.2,139.4,140.5,146.0,148.3. Anal.…”

“…HRMS Calcd. for C 12 9, 40.4, 48.2, 62.9, 63.4, 67.6, 76.6, 116.0, 116.2, 123.0, 123.1, 124.7, 126.1, 126.2, 127.1, 128.5, 128.7, 150.5, 151. 7,41.3,56.9,63.4,64.3,64.7,76.2,121.4,122.2,122.3,122.7,123.8,126.8,128.8,129.0,129.5,130.4,131.0,145.1,148.4;HRMS Calcd. for C 21 H 20 7,36.6,48.3,63.6,63.7,73.5,77.0,81.1,119.8,120.2,124.0,125.0,127.4,128.8,129.2,139.4,140.5,146.0,148.3.…”

“…The parent compound is synthesized from the naturally occurring amino acid trans-4-hydroxy-L-proline.5 Beak and Hoppe pioneered the directed lithiation of N-protected amines, 6 a procedure, which allows asymmetric induction in this step when the generally applicable secbutyllithium/(−)-sparteine system is employed for deprotonation. 7,8 In a recent communication we published the synthesis of novel C-substituted derivatives of (1S,4S)-2,5-diazabicyclo[2.2.1]heptane (1) (Scheme 1). This has been achieved by lithiation of the Boc-protected derivative 2 followed by the reaction with suitable electrophiles.…”