A self-condensation of aldehydes has been conveniently accomplished by the catalytic action of lysine in water or a solvent-free system under specific emulsion conditions to give α-branched α,β-unsaturated aldehydes in good yields.

Efficient methods for the resolution of various myo-inositol derivatives have been developed using O-acetylmandelic acid (OAM) as the chiral auxiliary. Various methods of introduction of the chiral auxiliary have been compared. DCC mediated coupling between the inositol derivative and O-acetylmandelic acid resulted in substantial racemization even at 0 °C; while acylation with O-acetylmandeloyl chloride in the presence of pyridine gave the diastereomers without any racemization of the chiral auxiliary. The advantage of using OAM as a chiral auxiliary is that the absolute configuration of the resolved diastereomers can be determined by analyzing the 1H NMR chemical shifts of various protons. The diastereomeric separation has been achieved either by fractional crystallization or column chromatography. The enantiomers of inositol derivatives could be obtained by the removal of chiral auxiliaries. By employing the known selective protection–deprotection strategies, various derivatives in optically active form could be synthesized.L-3,6-Di-O-[(S)-O-acetylmandeloyl]-1,2:4,5-di-O-isopropylidene-myo-inositolC32H36O12[α]D25=+53.2 (c 1, CH2Cl2)D-3,6-Di-O-[(S)-O-acetylmandeloyl]-1,2:4,5-di-O-isopropylidene-myo-inositolC32H36O12[α]D25=+64.4 (c 1, CH2Cl2)L-3,6-Di-O-[(S)-O-acetylmandeloyl]-1,2-O-isopropylidene-myo-inositolC29H32O12[α]D25=+53 (c 1, CH2Cl2)D-3,6-Di-O-[(S)-O-acetylmandeloyl]-1,2-O-isopropylidene-myo-inositolC29H32O12[α]D25=+71 (c 1, CH2Cl2)D-3,6-Di-O-[(S)-O-acetylmandeloyl]-1,2:4,5-di-O-cyclohexylidene-myo-inositolC38H44O12[α]D = +65.0 (c 0.846, CHCl3)L-3,6-Di-O-[(S)-O-acetylmandeloyl]-1,2:4,5-di-O-cyclohexylidene-myo-inositolC38H44O12[α]D = +27.1 (c 0.258, CHCl3)D-3,6-Di-O-[(S)-O-acetylmandeloyl]-1,2-O-cyclohexylidene-myo-inositolC32H36O12[α]D = +67.0 (c 0.81, CHCl3)L-3,6-Di-O-[(S)-O-acetylmandeloyl]-1,2-O-cyclohexylidene-myo-inositolC32H36O12[α]D = +45.6(c 1.05, CHCl3)D-3-O-[(S)-O-Acetylmandeloyl]-1,2-O-cyclohexylidene-myo-inositolC22H28O9[α]D = +57.4 (c 1.22, CHCl3)D-1,2:4,5-Di-O-cyclohexylidene-myo-inositolC18H28O6[α]D = −26.0 (c 0.562, CHCl3)L-1,2:4,5-Di-O-cyclohexylidene-myo-inositolC18H28O6[α]D = +25.5 (c 0.548, CHCl3)D-1,2-O-Cyclohexylidene-myo-inositolC12H20O6[α]D = −27.1 (c 0.70, MeOH)L-1,2-O-Cyclohexylidene-myo-inositolC12H20O6[α]D = +26.9 (c 0.78, MeOH)Dibenzyl-{L-6-O-[(S)-O-acetylmandeloyl]-1,2-O-cyclohexylidene-3,4-O-(tetraisopropyldisiloxan-1,3-diyl)-myo-inositol}-5-phosphiteC48H67O12PSi2[α]D = +24.3 (c 1.56, CHCl3)Dibenzyl-{D-6-O-[(S)-O-acetylmandeloyl]-1,2-O-cyclohexylidene-3,4-O-(tetraisopropyldisiloxan-1,3-diyl)-myo-inositol}-5-phosphiteC48H67O12PSi2[α]D = +27.4 (c 1.06, CHCl3)Dibenzyl-{L-6-O-[(S)-O-acetylmandeloyl]-1,2-O-cyclohexylidene-3,4-O-(tetraisopropyldisiloxan-1,3-diyl)-myo-inositol}-5-phosphateC48H67O13PSi2[α]D = +41.7 (c 1.80, CHCl3)Dibenzyl-{D-6-O-[(S)-O-acetylmandeloyl]-1,2-O-cyclohexylidene-3,4-O-(tetraisopropyldisiloxan-1,3-diyl)-myo-inositol}-5-phosphateC48H67O13PSi2[α]D = +12.0 (c 1.34, CHCl3)L-1,2-O-Isopropylidene-myo-inositolC9H16O6[α]D25=+56 (c 0.25, MeOH)D-1,2:4,5-Di-O-isopropylidene-myo-inositolC12H20O6[α]D25=-21.8 (c 1, CH3CN)D-1,2-O-Isopropylidene-myo-inositolC9H16O6[α]D25=-50.0 (c 0.1, MeOH)L-1,2:4,5-Di-O-isopropylidene-myo-inositolC12H20O6[α]D25=+22.3 (c 1, CH3CN)

NMR analyses of O-acetylmandelate (OAM) esters of a variety of crowded and conformationally locked cyclitol derivatives and other alcohols were carried out to examine the reliability of the use of OAM as a chiral anisotropy reagent (CAR) for the determination of the absolute configuration of an alcohol. These experiments showed that OAM can be used as a reliable CAR even in the case of sterically crowded alcohols, but the use of this method in conformationally locked alcohols should be skeptical. Although OAM is a frequently used chiral auxiliary for the resolution of cyclitol derivatives, the absolute configuration of the resolved alcohol is usually determined by converting it to a derivative of already known absolute configuration. The present study suggests that just the NMR analysis of the resolved diastereomers is sufficient enough to deduce the absolute configuration of these resolved cyclitol derivatives to determine their absolute configurations. Many literature examples where OAM is used for the resolution of different alcohols are used to generalize the fact that OAM is more reliable than other frequently used CARs such as methoxy trifluoromethyl phenyl acetic acid (MTPA), methoxy phenyl acetic acid (MPA) and mandelate.

An efficient method for the resolution of myo-inositol 1,3,5-orthoformate has been developed. The triol, 1 was converted to diastereomers via reaction with (S)-O-acetylmandeloyl chloride. Conditions were optimized for a diastereomeric ratio of 7:3. Both the diastereomers could be separated by column chromatography. The absolute configurations of the diastereomers were determined by converting the less polar diastereomer to the known l-2,4-di-O-benzyl-myo-inositol. The utility of the resolved derivatives is illustrated by a short and efficient synthesis of d-myo-inositol-4-phosphate in four steps from myo-inositol.Graphicl-2,4-Di-O-[(S)-O-acetylmandeloyl]-myo-inositol 1,3,5-orthoformateC27H26O12[α]D25=+60 (c 1, CHCl3)Source of chirality: chemical resolutiond-2,4-Di-O-[(S)-O-acetylmandeloyl]-myo-inositol 1,3,5-orthoformateC27H26O12[α]D25=+65.7 (c 2, CHCl3)Source of chirality: chemical resolutionl-2,4-Di-O-benzyl-myo-inositolC20H24O6[α]D25=−28.9 (c 1, EtOH)Source of chirality: chemical resolutionBis-cyclohexylammonium d-myo-inositol-4-phosphateC18H39O9N2P[α]D25=+2 (c 2, H2O)Source of chirality: chemical resolution

An efficient method for the resolution of 1,2:4,5-di-O-isopropylidene-myo-inositol has been developed. The diketal was converted to diastereomeric 3,6-di-O-mandelates by the reaction with (S)-O-acetylmandeloyl chloride. Both the diastereomers could be separated by sequential crystallization in multi-gram quantities. The enantiomers of the diol were obtained by removal of the chiral auxiliaries. Also the trans-isopropylidene was cleaved efficiently to obtain another pair of chiral diols.Graphicd-1,4-Di-O-[(S)-O-acetylmandeloyl]-2,3:5,6-di-O-isopropylidene-myo-inositolC32H36O12[α]D25=+53.2 (c 1, CH2Cl2)d-3,6-Di-O-[(S)-O-acetylmandeloyl]-1,2:4,5-di-O-isopropylidene-myo-inositolC32H36O12[α]D25=+64.4 (c 1, CH2Cl2)d-1,4-Di-O-[(S)-O-acetylmandeloyl]-2,3-O-isopropylidene-myo-inositolC29H32O12[α]D25=+53 (c 1, CH2Cl2)d-3,6-Di-O-[(S)-O-acetylmandeloyl]-1,2-O-isopropylidene-myo-inositolC29H32O12[α]D25=+71 (c 1, CH2Cl2)l-1,2:4,5-Di-O-isopropylidene-myo-inositolC12H20O6[α]D25=+22.3 (c 1, CH3CN)