the long - appreciated 
 beneficial properties of the trifluoromethyl 
 group in medicinal chemistry and the imperatives of green chemistry provide the impetus for the 
 current resurgence of interest in the development of trifluoromethylation 
 methods . the ability to produce ever more complex trifluoromethylated substances 
 gives rise to the need for efficient methods to unambiguously assign 
 their constitution , configuration , and conformation . current projects 
 in our laboratory necessitated the synthesis and configurational assignment 
 of pairs of diastereomeric -trifluoromethylcyclohexanols and 
 related compounds . prakash reagent or other systems delivering a nucleophilic cf3 moiety with cyclohexanones , it became apparent that assigning the configuration 
 relative to an existing stereogenic center in such compounds is not 
 straightforward in the absence of crystals suitable for x - ray analysis . thus , in previous work , the relative configuration of diastereomeric 
 pairs of -trifluoromethyl tertiary alcohols , if assigned at 
 all , was based on considerations of relative polarities , differences 
 in ir stretching frequencies of the oh group , nmr chemical shift differences 
 of the tertiary alcohols or of their derivatives , noe measurements 
 of derivatives , and considerations of inherent face selectivity in 
 the precursors . to address this problem , we considered two potential solutions : 
 ( i ) the application of heteronuclear noe - type experiments ( hoesy ) 
 between the cf3 group and proximal substituents and ( ii ) 
 the karplus - type correlation of the dihedral angle (  ) subtended by the 
 cf3 group and axial or equatorial hydrogen atoms at the 
 vicinal position ( h - c - c - cf3 ) 
 with the jch heteronuclear 
 coupling constants ( figure 1 ) . heteronuclear jch coupling constants are widely 
 applied in carbohydrate chemistry for the determination of glycosidic 
 bond and hydroxymethyl group torsion angles and also enable the determination of torsion angles about cc however , with the exception of 
 their use for the configurational assignment of sialic acid glycosides , heteronuclear jch coupling 
 constants do not find wide application in the conformational analysis 
 of cyclic systems . we report here on the successful development of a straightforward jch heteronuclear coupling method 
 for the determination of configuration in trifluoromethylated tertiary 
 alcohols and related compounds that we believe will also be of use 
 in determining the relative configuration of a broad range of cf3-bearing quaternary centers . we also report related vicinal c  h coupling constants in olefinic systems , 
 which should apply in the assignment of configuration of trifluoromethyl 
 alkenes . reaction 
 of the ruppert  prakash reagent 
 with a series of representative cyclohexanones 16 in the presence of either tetrabutylammonium fluoride or 
 cesium fluoride gave rise to the -trifluoromethylated cyclohexanols 
 or the corresponding trimethylsilyl ethers 914 with the yields and selectivities listed in table 1 , entries 16 . similarly , reaction of the 
 ruppert  prakash reagent with gluconolactone 7 gave 
 ketose 15 ( table 1 , entry 7 ) . prakash reagent with imine 8 , formed in situ from 4-tert - butylcyclohexanone 
 and benzylamine followed by hydrogenolysis , gave 
 diastereoisomeric -trifluoromethylamines 16 ( table 1 , entry 8) . reaction of pentafluoroethyltrimethylsilane with 4-tert - butylcyclohexanone 
 catalyzed by tetrabutylammonium fluoride gave -pentafluoroethyl 
 4-tert - butylcyclohexanols 17 ( table 1 , entry 9 ) . all reactions , with the exception 
 of entry 9 , were conducted with 2.0 equiv of tmscf3 in 
 thf in the presence of 0.1 equiv of either tbaf or csf . promoted with tbaf and worked up 
 with 6 n hcl . promoted with csf 
 and worked up 
 with 2 equiv of tbaf . promoted 
 with 0.8 equiv of khf2 and 1.5 equiv of tmscf3 in acetonitrile , followed 
 by hydrogenolysis over pd / c in meoh . 3.0 equiv of tmscf2cf3 in thf in 
 the presence of 0.3 equiv tbaf was employed . in addition , a diastereomeric mixture of two steroids 19 containing a quaternary carbon , in which one of the four 
 ligands 
 is a trifluoromethyl group , was prepared as described by blazejewski 
 and co - workers by radical reaction of 
 allyltrimethylstannane with s - methyl xanthate ester 18 derived from tertiary trimethylsilyl 
 ether 11 ( scheme 1 ) . although it is not the 
 primary focus of this article , it is noteworthy and bears comment 
 that kinetically controlled reaction of the ruppert prakash 
 reagent with five of the six cyclohexanones studied is selective for 
 the formation of the axial trifluoromethyl derivatives . the use of 
 both 4-tert - butyl and 4-phenylcyclohexanone as substrate 
 gave approximate 4:1 mixtures of adducts favoring introduction of 
 the cf3 group syn to the remote substituent , with the products 
 retaining essentially undistorted chair conformations in the solution 
 phase , as determined by analysis of the h nmr spectra , 
 despite the axial location of the bulky cf3 group . previously , 
 the major product from the reaction with 4-phenylcyclohexanone was 
 assigned the opposite configuration ( cf3 trans to phenyl ) 
 on the basis of chemical shift differences in the derived xanthate 
 esters of the two isomers . in view of 
 this discrepancy and in support of the fdcs nmr method discussed below , 
 we obtained an x - ray crystal structure of the major isomer from reaction 
 with 4-phenylcyclohexane ( supporting information and ccdc 1032684 ) , which confirms its chair conformation and the 
 axial location of the cf3 group . this assignment corrects the earlier literature , focuses attention on the ambiguities arising from the assignment 
 of configuration in such -trifluoromethyl tertiary alcohols 
 on the basis of chemical shift arguments alone , and underlines the 
 need for unambiguous methods for assignment of configuration that 
 are preferably based on the analysis of coupling constants . in their original report on the reaction of trifluoromethyltrimethysilane 
 with aldehydes and ketones , prakash and co - workers noted the formation 
 of a single , but unassigned , diastereomeric product in the reaction 
 with cholestanone 3 . subsequent 
 workers reported a 96:4 ratio of isomers favoring the 3-cf3 epimer , but they did not provide any basis for the attribution 
 of configuration . in our hands , a single 
 diastereomer 11 was formed ( table 1 , entry 3 ) , to which we assign the 3-cf3 configuration 
 on the basis of the fdcs method discussed below and which is further 
 confirmed by hoesy . similarly , triterpenoid methyl ester 4 gives a single isomer of adduct 12 with an axial cf3 group ( table 1 , entry 4 ) , as determined 
 by fdcs and confirmed by the hoesy relationship of the cf3 group to a single of the two vicinal methyl groups . the glucopyranose-4-one 
 derivative 5 reacts in a highly selective manner with 
 the ruppert prakash reagent , but it affords galacto - configured 
 trimethylsilyl ether 13 with the equatorial cf3 group ( table 1 , entry 5 ) . the configuration 
 of this derivative was assigned by the fdcs method below and is confirmed 
 by noesy correlations between the trimethylsilyl methyl groups and 
 the axial hydrogen at position 2 as well as by hoesy correlations 
 between the cf3 group and the axial hydrogens at positions 
 3 and 5 . with apramycinone derivative 6 , as reported 
 previously , a return to axial selectivity 
 is observed ( table 1 , entry 6 ) , as confirmed 
 by hoesy measurements . the axial selectivity observed for the 
 introduction of the cf3 group into cyclohexanones 14 and 6 is interesting 
 in view of the steric bulk of 
 the cf3 group itself ( steric a value 2.37 ) and , more pertinently , of the presumed pentacoordinate 
 species ( r2co - sime3-cf3 or f - sime3-cf3 ) that transfers the cf3 group to the ketone . presumably , 
 this selectivity arises from the coordination / activation of the ketone 
 to the trimethylsilyl group of the ruppert prakash reagent , 
 as suggested by prakash and yudin ; in 
 much the same way , the facial selectivity of alkyllithium attack on 
 cyclohexanones can be reversed from the equatorial face to the axial 
 face by complexation of the ketone with sterically bulky lewis acids . the equatorial selectivity observed in the formation 
 of 13 is consistent with that observed for the addition 
 of the bulky trichloromethide anion to 13 and it is -anomer and for the reduction of the permethyl analogue 
 of 13 by sodium borodeuteride . less hindered acetylide nucleophiles , on the other hand , are axial 
 selective in their reactions with 13 . the single diastereomer observed in the formation of the 
 six - membered cyclic -trifluoromethyl hemiacetal 15 presumably is due to mutarotation subsequent to the initial attack 
 and so reflects both the steric bulk of the cf3 group and the influence of the anomeric effects . the reduced selectivity observed in the 
 trifluoromethylation of 
 the n - benzylimine 8 , as compared to 
 reaction with the corresponding ketone 1 ( table 1 , entries 1 and 8) , presumably arises from the weaker 
 coordination of the imine nitrogen than the ketone oxygen to the reagent , 
 resulting in a smaller effective bulk and more facile accommodation 
 of the c consistent with the 
 greater steric bulk of the pentafluoroethyl group ( steric a value 
 2.67 ) , reaction of 4-tert - butylcyclohexanone 1 with pentafluoroethyltrimethylsilane ( table 1 , entry 9 ) was 
 less selective than that with trifluoromethyltrimethylsilane ( table 1 , entry 1 ) , resulting in a greater proportion of 
 adduct 17 with the equatorial fluoroalkyl group . in the sialic acids , the measurement of jch coupling constants between 
 the anomeric carboxyl carbon and the axial h3 is a rapid and reliable 
 method for the determination of anomeric configuration ( figure 2 ) . such experiments , which we dub single frequency off - resonance decoupling 
 ( sford ) and which are a variation on standard , off - resonance decoupling methods , 
 are usually conducted on the methyl esters and are carried out with 
 selective low - power decoupling of the methoxycarbonyl protons to facilitate 
 identification of the desired residual jch coupling constant in the c nmr spectrum , 
 as illustrated in figure 3a . an axial co2me group , with its antiperiplanar relation to the axial h3 , 
 typically displays a vicinal coupling constant of 57 hz , whereas 
 its equatorial counterpart , flanked by two gauche hydrogens , is usually 
 devoid of coupling ( figure 2 ) . inspired by this method , we developed an analogous protocol 
 for 
 the determination of jch coupling 
 constants between the carbon of a cf3 group and its vicinal 
 hydrogen atoms , which we dub the c  h fluorine - decoupled spectroscopy ( fdcs ) method . in this experiment , 
 a fully h - coupled , c - observed spectrum was 
 acquired with selective f irradiation , as illustrated 
 in figure 3b . in this manner , the cf3 resonance is observed to be free of jcf coupling , thereby revealing 
 the diagnostic jch couplings 
 in an unobstructed manner . pulse sequences employed in the sford and fdcs 
 determinations and 
 in the confirmatory hoesy experiments . ( a ) pulse sequence for single 
 frequency off - resonance decoupling ( sford ) experiment . c was the observed nucleus , and the desired h was irradiated 
 with low - power single frequency continuous wave ( cw ) pulse . c spectrum was the observed nucleus , and f signal 
 was selectively decoupled with a waltz-16 composite decoupling scheme . the standard pulse sequence from the vnmrj 3.2 software 
 library was used , with 0.3 s mixing time and 4.0 s relaxation delay . the acquisition time was 0.17 s , with 16 or 32 scans for each of 128 
 increments . ( d ) pulse sequence for the h{f } 1d hoesy experiment . the standard pulse sequence from 
 the vnmrj 3.2 software library was used . f noe difference 
 experiment , two fids were recorded : one with f selective 
 low - power irradiation and the second fid without f irradiation . the resulting two spectra were subtracted digitally to observe the 
 h  f noe spectrum . application of the fdcs method to the various -trifluoromethyl 
 cycloalkanols or their trimethylsilyl ethers displayed in table 2 supports the initial premise that the c  h heteronuclear coupling constant is a function 
 of the torsion angle . thus , an axial cf3 group exhibits 
 a coupling constant of 7.39.8 hz with vicinal axial hydrogen 
 atoms (  180 ) ( table 2 , entries 
 1 , 3 , 5 , 6 , and 8) . the vicinal coupling constant between an axial 
 cf3 group and an equatorial hydrogen atom (  60 ) 
 is typically 1 hz , but it ranges as high as 4.2 hz in the 
 steroidal and triterpenoid examples ( table 2 , entries 1 , 3 , 5 , 6 , and 8) . an equatorial cf3 group 
 exhibits a vicinal coupling constant of 1 hz with vicinal 
 axial and equatorial hydrogen atoms (  60 ) in the systems 
 studied ( table 2 , entries 2 , 4 , 7 , 9 , and 10 ) . 
 in the case of both the 180 and 60 dihedral angles , the 
 larger coupling constants in the observed ranges are found in the 
 conformationally more rigid systems ( table 2 , entries 5 and 6 ) . this suggests that the smaller coupling constants 
 observed in the simple cyclohexyl systems are the result of an appreciable 
 population of nonchair conformers at room temperature , consistent 
 with the most recent estimates of the steric a value for the cf3 group , which suggest that it is more bulky than an isopropyl 
 group but less so than a tert - butyl group . although the present data set is not sufficiently 
 extensive for careful calibration , we note that , as is well - appreciated 
 in homonuclear jh , h coupling and as has been demonstrated in other heteronuclear jch systems , the general karplus - type relationship correlating the magnitude 
 of f3c - c - c - h coupling constant 
 with torsion angle will be modulated by the nature and orientation 
 of substituents . the fdcs method is readily extended from trifluoromethylcyclohexanols 
 to trifluoromethylcyclohexylamines and allows the assignment of axial 
 and equatorial cf3 groups in the -trifluoromethyl 
 amines 16 ( table 2 , entries 11 
 and 12 ) . by way of example , figure 4 shows 
 the c resonances of the two cf3 groups in 
 a mixture of the diastereomeric amines 16 before ( figure 4a ) and after ( figure 4b ) 
 decoupling of the f atoms . cf3 resonances in a diasteromeric mixture 
 of trifluoromethylamines 16 before ( a ) and after ( b ) f decoupling with a partial expansion ( c ) . the analysis of the fdcs spectra of the inseparable 
 diastereomeric 
 trifluoromethylated steroid derivatives 19 , in which 
 the trifluoromethyl group is appended to a quaternary carbon , were 
 complicated by the additional jch coupling of the cf3 resonances to the allylic 
 methylene protons in addition to the diagnostic couplings to the vicinal 
 hydrogens in the steroidal a ring ( table 2 , 
 entries 15 and 16 ; figure 5 ) . nevertheless , 
 application of the standard fdcs sequence to the standard c spectrum ( figure 5a ) gave a simplified spectrum 
 ( figure 5b ) displaying a downfield cf3 resonance as a broad multiplet for one isomer and a narrower more 
 upfield multiplet for the second isomer . the broader multiplet , expanded 
 in figure 5c , clearly represents the axial 
 cf3 group with its diaxial couplings to the axial hydrogens 
 at the vicinal 2- and 4-positions , whereas the narrower multiplet 
 lacks such large couplings to the vicinal hydrogens in the steroidal 
 a ring . although both multiplets are convoluted with additional jch couplings to the two allylic 
 hydrogens , which renders actual measurement of the diagnostic jch couplings constants difficult , 
 the clear difference in the width at half height of the two multiplets 
 ( w1/2 = 17.2 and 26.3 hz ) allows relative 
 configuration to be assigned . to confirm this assignment , a sford 
 experiment was conducted in which the allylic hydrogens were selectively 
 decoupled , giving rise to the partial spectrum in figure 5d . the signals in this sford experiment retain the 
 quartet due to coupling to the cf3 resonances and also display coupling to the vicinal hydrogens 
 at positions 2 and 4 in the a ring . the lines that make up the more 
 downfield quartet are broader than those in the upfield quartet , as 
 they display the larger jch couplings to the axial hydrogens at the 2- and 4-positions , which 
 is observable on the expansion ( figure 5e ) . further confirmation of these assignments was achieved by noesy experiments 
 showing the spatial proximity of the vinylic hydrogens with the axial 
 hydrogen at the 1-position in the a ring of the major isomer . cf3 resonances in a diasteromeric mixture 
 of trifluoromethylsteroids 19 : ( a ) before f decoupling , ( b ) after f decoupling , ( c ) expansion 
 of panel b. ( d ) c sford experiment , and ( e ) expansion 
 of panel d. the fdcs method is not 
 limited to cf3 groups , 
 as demonstrated by its application to the diastereomeric -pentafluoroethyl 
 cyclohexanols 17 ( table 2 , entries 
 13 and 14 ) involving observation of the cf2 resonance . the fdcs spectra of the two isomers of 17 contain an additional jcf quartet coupling to the cf3 group , but as the extra coupling 
 constant is significantly larger , it is of no consequence and does 
 not complicate interpretation . the fdcs method was also applied to 
 the known -mono- and di- fluoromethylcyclohexanols 20 and 21 ( table 2 , entries 1720 ) , 
 which were donated by drs . the spectra of 20 and 21 are complicated by convolution of the vicinal coupling 
 constants with the jch couplings , 
 but spectral interpretation is not difficult , as the vicinal coupling 
 constants are more than an order of magnitude smaller . commercially 
 available -trifluoromethyl ethanol 22 allowed 
 the determination of the c  h vicinal 
 coupling constant between a hydrogen atom and a cf3 group 
 in a freely rotating acyclic system ( table 2 , entry 21 ) . unless otherwise 
 stated , spectra 
 were recorded in cdcl3 . the descriptors ax and eq refer 
 to the axial or equatorial location of the fluoroalkyl groups and 
 of the vicinal hydrogens to which they are coupled , respectively . owing to complications arising from 
 convolution with additional cf coupling to the allylic 
 hydrogens , multiplicity and coupling constants are difficult to assign 
 for 19ax and 19eq ( see text for clarification ) . as discussed above ( table 2 ) , 
 the configuration of a number of the samples 
 employed in this study was confirmed by heteronuclear overhauser effect 
 ( hoesy ) measurements between cf3 groups and spatially proximal 
 hydrogen atoms . hoesy spectra were acquired using an autotriple 
 resonance broadband probe ( atb ) , which is simultaneously tuned to h and f on the high - band rf coil . 2d hoesy experiments 
 used the manufacturer supplied fh - hoesy pulse sequence implemented 
 in vnmrj 3.2 software ( figure 3c ) . h - observed , f - irradiated 1d hoesy experiments used the 
 fh decoupling pulse sequence from the vnmrj 3.2 software ( figure 3d ) . the main limitation of the hoesy method , as 
 implemented in these experiments , is the requirement for the three 
 channel or atb type probe and of a spectrometer with three channel 
 capabilities . when such hardware is on hand , the hoesy method , 1d 
 or 2d , provides a rapid means of assessing the spatial proximity of 
 the cf3 and adjacent protons and therefore of inferring 
 configuration and/or conformation . because the 1d hoesy sequence is 
 observed by the proton channel and the 2d hoesy sequence by the f channel , sensitivity is correspondingly high and data acquisition 
 times are relatively short . the fdcs sequence , on the other hand , 
 employs a standard two - channel probe and can be implemented on any 
 modern spectrometer . it gives direct information on the dihedral angle 
 subtended by the coupled h and cf3 spins and therefore on the conformation and/or configuration 
 of the substance under investigation . the fdcs spectrum is acquired 
 through the c channel , and data acquisition is correspondingly 
 slow . overall , fdcs and hoesy provide complementary information , and 
 the combination of the two is a powerful tool for studying the configuration 
 and conformation of cf3 and other fluoroalkyl - containing 
 molecules . although 
 the primary focus of this investigation is the development of the 
 fdcs method for the assignment of configuration in saturated systems 
 carrying cf3 groups , using commercially available compounds , 
 we also briefly investigated its application to unsaturated molecules . thus , as illustrated in figure 6 , the fdcs 
 method allows distinction of regioisomers in trifluoromethylated arenes , 
 as the cf3 group exhibits a measurable c  h coupling only to an ortho - hydrogen . likewise , 
 the fdcs method may be applied to the determination of configuration 
 of trifluoromethyl - substituted alkenes , as the trans - jch coupling constant is 
 more than double that of the corresponding cis coupling 
 constant ; jch couplings are 
 even smaller and should not complicate assignment of configuration 
 ( figure 6 ) . the 
 fluorine - decoupled carbon spectroscopy method is readily implemented 
 on standard two - channel nmr spectrometers and provides a facile method 
 for the determination of the configuration and/or conformation of 
 cf3- and other fluoroalkyl - substituted molecules . based 
 on the karplus - type relation of the h - c - c - cf3 torsion angle to the coupling constant , the method 
 is an alternative to h , f hoesy . earlier methods 
 for the assignment of configuration of cf3-substituted 
 tertiary alcohols based on chemical shift differences in derived xanthate 
 esters are unreliable and should be succeeded by the fdcs and/or hoesy 
 methods . all reactions were performed using 
 oven - dried glassware under an atmosphere of argon . all reagents and 
 solvents were purchased from commercial suppliers and were used without 
 further purification unless otherwise specified . reactions were monitored by analytical thin - layer chromatography on 
 precoated glass - backed plates ( w / uv 254 ) and visualized by uv irradiation 
 ( 254 nm ) or by staining with 25% h2so4 in etoh 
 or ceric ammonium molybdate solution . high - resolution 
 mass spectra were recorded with an electrospray source coupled to 
 a time - of - flight mass analyzer . h , c , f , hoesy , and fdcs spectra were recorded on a 400 or 600 
 mhz spectrometer using vnmrj 3.2 as processing software . chemical shifts 
 are given in ppm (  ) , and coupling constants j are given in hz . compounds 9ax and 9eq were prepared according to a literature 
 protocol using 4-tert - butylcyclohexanone 
 ( 400 mg , 2.6 mmol ) and ( trifluoromethyl)trimethylsilane ( 740 mg , 5.2 
 mmol ) in tetrahydrofuran ( 3.0 ml ) at room temperature with a catalytic 
 amount of tetrabutylammonium fluoride ( 0.25 ml , 1.0 m in tetrahydrofuran ) . chromatographic purification ( gradient elution of diethyl ether / pentane : 
 2 to 10% ) gave 9eq ( 70 mg , 12% , mp 48.049.5 c ) 
 as an off - white solid and 9ax ( 290 mg , 50% , mp 94.595.5 
 c ) as a white solid . 9eq : h nmr 
 ( 600 mhz , cdcl3 ) :  1.82 ( dd , j = 
 14.3 , 2.2 hz , 2h ) , 1.73 ( br s , 1h ) , 1.67 ( m , 2h ) , 1.59 ( dt , j = 13.5 , 4.0 hz , 2h ) , 1.36 ( m , 2h ) , 1.00 ( tt , j = 12.1 , 2.9 hz , 1h ) , 0.88 ( s , 9h ) ; c nmr ( 150 mhz , 
 cdcl3 ) :  126.0 ( q , jcf = 284.4 hz , cf3 ) , 72.2 ( q , jcf = 28.1 hz , c1 ) , 47.0 , 32.3 , 30.2 , 
 27.3 , 21.1 ; f nmr ( 564 mhz , cdcl3 ) :  
 87.4 ( s , cf3 ) ; fdcs ( 150 ) mhz , cdcl3 ) :  131.5 ( br s ) . 9ax : h nmr 
 ( 600 mhz , cdcl3 ) : 
  2.20 ( m , 3h ) , 1.70 ( d , j = 13.5 hz , 2h ) , 
 1.48 ( dt , j = 13.9 , 2.2 hz , 2h ) , 1.30 ( q , j = 12.4 hz , 2h ) , 1.08 ( tt , j = 12.1 , 2.9 
 hz , 1h ) , 0.84 ( s , 9h ) ; c nmr ( 150 mhz , cdcl3 ) :  126.8 ( q , jcf = 
 286.1 hz , cf3 ) , 71.8 ( q , jcf = 27.5 hz , c1 ) , 46.3 , 33.3 , 32.2 , 27.4 , 
 23.0 ; f nmr ( 564 mhz , cdcl3 ) : 80.4 
 ( s , cf3 ) ; fdcs ( 150 mhz , cdcl3 ) :  131.5 
 ( tt , j = 8.9 , 3.6 hz ) . compounds 10ax and 10eq were prepared according to a literature 
 protocol using 4-phenylcyclohexanone 
 ( 1.0 g , 5.7 mmol ) and ( trifluoromethyl)trimethylsilane ( 1.6 g , 11.2 
 mmol ) in tetrahydrofuran ( 5.0 ml ) at room temperature with a catalytic 
 amount of tetrabutylammonium fluoride ( 0.6 ml , 1.0 m in tetrahydrofuran ) . the residue was purified by column chromatography ( eluting with dichloromethane ) 
 followed by recrystallization from 2-propanol / water ( 7:1 ) to give 10eq ( 90 mg , 8% , mp 75.076.5 c ) as an off - white 
 solid , 10ax ( 356 mg , 24% , mp 70.571.3 c ) 
 as a white solid , and a mixture of both isomers ( 750 mg , 52% ) . 10eq : h nmr ( 600 mhz , cdcl3 ) : 
  7.33 ( t , j = 7.7 hz , 2h ) , 7.25 ( m , 3h ) , 2.55 
 ( tt , j = 11.7 , 4.0 hz , 1h ) , 1.93 ( m , 3h ) , 1.85 ( m , 
 6h ) ; c nmr ( 150 mhz , cdcl3 ) :  146.1 , 
 125.5 , 126.7 , 126.6 ( q , jcf = 284.4 hz , cf3 ) , 126.3 , 72.0 ( q , jcf = 28.1 hz , c1 ) , 43.2 , 30.1 , 27.7 ; f nmr ( 564 mhz , cdcl3 ) :  87.3 ( s , 
 cf3 ) ; fdcs ( 150 mhz , cdcl3 ) :  131.5 ( br 
 s ) . 10ax : h nmr ( 600 mhz , cdcl3 ) :  7.33 ( m , 2h ) , 7.26 ( m , 3h ) , 2.77 ( br s , 1h ) , 2.18 
 ( m , 
 3h ) , 1.96 ( m , 4h ) , 1.69 ( m , 2h ) ; c nmr ( 150 mhz , cdcl3 ) :  144.7 , 128.5 , 126.8 , 126.7 ( q , jcf = 285.5 hz , cf3 ) , 126.1 , 72.0 
 ( q , jcf = 25.8 hz , c1 ) , 40.4 , 31.0 , 28.0 ; f nmr ( 564 mhz , cdcl3 ) :  82.2 ( s , cf3 ) ; fdcs ( 150 mhz , cdcl3 ) :  124.2 ( t , j = 7.3 hz ) . to a stirred solution of cholestan-3-one 
 ( 400 mg , 1.0 mmol ) in tetrahydrofuran ( 3.0 ml ) were added ( trifluoromethyl)trimethylsilane 
 ( 300 mg , 2.1 mmol ) and a catalytic amount of tetrabutylammonium fluoride 
 ( 27 mg , 0.1 mmol , 1.0 m in tetrahydrofuran ) at room temperature . the 
 resulting reaction mixture was stirred at room temperature for 2 h. 
 the solvent was evaporated under reduced pressure , and the residue 
 was dissolved in dichloromethane ( 5.0 ml ) , washed with water followed 
 by brine , dried over na2so4 , and concentrated 
 under reduced pressure . the residue was purified by column chromatography 
 on silica gel eluting with etoac / hexanes ( 2 to 10% ) to afford 11ax(38 ) ( 482 mg , 90% , mp 103104 
 c ) as a white solid . [ ]d20 = + 20.4 ( c = 3.7 , dichloromethane ) ; h nmr ( 600 mhz , cdcl3 ) :  2.08 ( td , j = 14.6 , 1.8 hz , 1h ) , 1.95 ( td , j = 12.8 , 
 2.9 hz , 1h ) , 1.851.77 ( m , 2h ) , 1.65 ( m , 2h ) , 1.611.42 
 ( m , 6h ) , 1.391.29 ( m , 6h ) , 1.281.20 ( m , 3h ) , 1.200.94 
 ( m , 11h ) , 0.89 ( d , j = 6.6 hz , 3h ) , 0.86 ( d , j = 2.6 hz , 3h ) , 0.83 ( s , 3h ) , 0.67 ( dd , j = 12.4 , 4.0 hz , 1h ) , 0.64 ( s , 3h ) , 0.14 ( s , 9h ) ; c 
 nmr ( 150 mhz , cdcl3 ) :  126.6 ( q , jcf = 287.2 hz , cf3 ) , 75.2 ( q , jcf = 26.9 hz , c3 ) , 
 56.3 , 56.2 , 53.9 , 42.6 , 41.8 , 39.9 , 39.5 , 36.8 , 36.1 , 35.8 , 35.4 , 
 35.2 , 34.8 , 31.7 , 30.1 , 28.6 , 28.2 , 27.9 , 24.1 , 23.8 , 22.8 , 22.6 , 
 21.1 , 18.6 , 12.0 , 11.7 , 2.2 ; f nmr ( 564 mhz , cdcl3 ) :  80.3 ( s , cf3 ) ; fdcs ( 150 mhz , 
 cdcl3 )  : 131.5 ( tt , j = 9.6 , 4.1 
 hz ) . a solution of methyl 3-ketoolean-12-en-28-oate ( 40 mg , 0.08 mmol ) and ( trifluoromethyl)trimethylsilane 
 ( 66.2 mg , 0.46 mmol ) in tetrahydrofuran ( 1.5 ml ) was treated with 
 a catalytic amount of tetrabutylammonium fluoride ( 4.4 mg , 0.02 mmol , 
 1.0 m in tetrahydrofuran ) at room temperature . the resulting reaction 
 mixture was stirred at room temperature for 1 h. the solvent was evaporated 
 under reduced pressure , and the residue was dissolved in dichloromethane 
 ( 2.0 ml ) , washed with water followed by brine , dried over na2so4 , and concentrated under reduced pressure . the residue 
 was subjected to flash column chromatography ( gradient elution of 
 etoac / hexanes : 2 to 20% ) to afford 12ax ( 42 mg , 82% , 
 mp 178179 c ) as a white solid . [ ]d20 = + 62.1 ( c = 1.4 , dichloromethane ) ; h nmr ( 600 mhz , cdcl3 ) :  5.26 ( t , j = 3.6 hz , 1h ) , 3.60 
 ( s , 3h ) , 2.84 ( dd , j = 13.9 , 4.4 hz , 1h ) , 1.991.78 
 ( m , 5h ) , 1.701.54 ( m , 5h ) , 1.51 ( m , 2h ) , 1.44 ( m , 2h ) , 1.31 
 ( m , 3h ) , 1.24 ( m , 2h ) , 1.18 ( t , j = 12.2 hz , 2h ) , 
 1.12 ( m , 1h ) , 1.11 ( s , 3h ) , 0.96 ( br s , 3h ) , 0.94 ( s , 3h ) , 0.91 ( s , 
 3h ) , 0.88 ( s , 3h ) , 0.82 ( s , 3h ) , 0.71 ( s , 3h ) , 0.11 ( s , 9h ) ; c nmr ( 150 mhz , cdcl3 ) :  178.2 , 143.8 , 
 127.2 ( q , jcf = 291.7 hz , 
 cf3 ) , 122.1 , 81.0 ( q , jcf = 24.6 hz , c3 ) , 51.4 , 51.2 , 47.5 , 46.7 , 45.8 , 
 41.7 , 41.6 , 41.3 , 39.2 , 36.3 , 35.4 , 33.8 , 33.0 , 32.8 , 32.3 , 30.6 , 
 27.7 , 24.1 , 23.5 , 23.3 , 23.0 , 21.1 , 19.1 , 16.9 , 15.5 , 2.1 ; f nmr ( 564 mhz , cdcl3 ) :  69.5 ( s , cf3 ) ; fdcs ( 150 mhz , cdcl3 ) :  124.6 ( dd , j = 9.8 , 3.1 hz ) ; esihrms calcd for c35h57o3f3sina ( [ m + na ] ) , 633.3916 ; 
 found , 633.3927 . to a solution of methyl 2,3,6-tri - o - benzyl--d - glucopyranoside ( 296 mg , 0.54 mmol ) in anhydrous dichloromethane ( 2.5 ml ) was added 
 dess - martin periodinane ( 296 mg , 0.69 mmol ) at room temperature . the 
 resulting reaction mixture was stirred at room temperature for 3 h , 
 quenched with saturated aqueous nahco3 ( 3.0 ml ) , and washed 
 with water ( 3.0 ml ) and brine ( 3.0 ml ) . the solvent was evaporated 
 under reduced pressure to give the 4-ketone as yellow oil , which was 
 taken forward to the next step without further characterization . to 
 a solution of this ketone ( 220 mg , 0.47 mmol ) in anhydrous tetrahydrofuran 
 ( 4.0 ml ) was added a catalytic amount of cesium fluoride ( 7.0 mg , 
 0.04 mmol ) followed by ( trifluoromethyl)trimethylsilane ( 700 mg , 4.90 
 mmol ) at room temperature . the resulting reaction mixture was stirred 
 at room temperature for 1 h. the solvent was evaporated under reduced 
 pressure , and the residue was dissolved in dichloromethane ( 5.0 ml ) , 
 washed with water ( 5.0 ml ) followed by brine ( 5.0 ml ) , dried over 
 na2so4 , and concentrated under reduced pressure . the residue was purified by silica gel column chromatography eluting 
 with 10% etoac in hexanes to give 13eq ( 198 mg , 69% ) 
 as an oil . [ ]d25 = + 36.5 ( c= 4.9 , dichloromethane ) ; h nmr ( 600 mhz , cdcl3 ) :  7.387.25 
 ( m , 15h ) , 4.97 ( dd , j = 9.9 , 5.1 hz , 2h ) , 4.74 ( d , j = 10.6 hz , 1h ) , 4.64 ( d , j = 11.7 hz , 
 1h ) , 4.60 ( d , j = 9.9 hz , 1h ) , 4.54 ( d , j = 11.7 hz , 1h ) , 4.33 ( d , j = 7.7 hz , 1h ) , 3.96 
 ( dd , j = 11.4 , 2.2 hz , 1h ) , 3.81 ( dd , j = 7.3 , 2.2 hz , 1h ) , 3.74 ( d , j = 9.5 hz , 1h ) , 3.69 
 ( dd , j = 11.3 , 7.7 hz , 1h ) , 3.65 ( d , j = 9.2 hz , 1h ) , 3.64 ( s , 3h ) , 0.04 ( s , 9h ) ; c nmr ( 150 
 mhz , cdcl3 ) :  138.3 , 138.1 , 137.5 , 128.7 , 128.4 , 
 128.3 , 128.2 , 128.1 , 127.7 , 127.7 , 127.6 , 127.6 , 124.6 ( q , jcf = 291.1 hz , cf3 ) , 104.5 , 
 80.3 , 79.5 , 78.5 ( q , jcf = 
 25.2 hz , c4 ) , 76.4 , 75.6 , 74.8 , 73.7 , 69.3 , 57.2 , 1.8 ; f nmr ( 564 mhz , cdcl3 ) :  64.7 ( s , 
 cf3 ) ; fdcs ( 150 mhz , cdcl3 ) :  122.1 ( d , j = 1.1 hz ) ; esihrms calcd for c32h39o6f3sina ( [ m + na ] ) , 627.2366 ; 
 found , 627.2341 . to a solution of 
 2,3,4,6-tetra - o - benzyl - d - glucono-1,5-lactone ( 200 mg , 0.47 mmol ) in anhydrous tetrahydrofuran 
 ( 4.0 ml ) , was added a catalytic amount of cesium fluoride ( 6.0 mg , 
 0.04 mmol ) followed by ( trifluoromethyl)trimethylsilane ( 1.0 g , 7.40 
 mmol ) at room temperature . the resulting reaction mixture was stirred 
 at room temperature for 1 h. the solvent was evaporated under reduced 
 pressure , and the residue was dissolved in dichloromethane ( 4.0 ml ) , 
 washed with water ( 4.0 ml ) followed by brine ( 4.0 ml ) , dried over 
 na2so4 , and concentrated under reduced pressure . the residue was dissolved in tetrahydrofuran ( 3.0 ml ) and was treated 
 with tetrabutylammonium fluoride ( 170 mg , 0.65 mmol , 1.0 m in thf ) 
 at room temperature . the solvent was evaporated under reduced 
 pressure , and the residue was purified by silica gel column chromatography 
 eluting with 10% etoac in hexanes to give 15eq ( 142 mg , 
 65% ) as an oil . [ ]d25 = + 50.3 ( c= 8.0 , dichloromethane ) ; h nmr ( 600 mhz , cdcl3 ) :  7.407.27 
 ( m , 17h ) , 7.267.22 ( m , 3h ) , 4.97 ( d , j = 
 11.0 hz , 1h ) , 4.90 ( d , j = 2.9 hz , 1h ) , 4.87 ( br 
 s , 1h ) , 4.85 ( d , j = 10.6 hz , 1h ) , 4.75 ( d , j = 9.9 hz , 1h ) , 4.69 ( dd , j = 10.6 , 7.7 
 hz , 1h ) , 4.59 ( d , j = 12.5 hz , 1h ) , 4.05 ( d , j = 9.9 hz , 1h ) , 3.94 ( br s , 1h ) , 3.93 ( d , j = 5.1 hz , 1h ) , 3.92 ( br s , 1h ) , 3.85 ( dd , j = 11.4 , 
 3.6 hz , 1h ) , 3.81 ( m , 1h ) , 3.76 ( dd , j = 11.7 , 1.8 
 hz , 1h ) ; c nmr ( 150 mhz , cdcl3 ) :  138.2 , 
 138.1 , 137.9 , 136.9 , 128.5 , 128.5 , 128.4 , 128.3 , 128.3 , 128.2 , 127.9 , 
 127.8 , 127.7 , 127.7 , 127.6 , 127.5 , 122.4 ( q , jcf = 287.2 hz , cf3 ) , 94.3 ( q , jcf = 31.9 hz , c1 ) , 83.4 , 78.3 , 76.8 , 
 75.9 , 75.7 , 75.1 , 73.4 , 72.9 , 67.8 ; f nmr ( 564 mhz , cdcl3 ) :  85.8 ( s , cf3 ) ; fdcs ( 150 mhz , 
 cdcl3 ) :  122.1 ( br s ) ; esihrms calcd for c35h35o6f3na ( [ m + na ] ) , 
 631.2283 ; found , 631.2264 . a suspension 
 of 4-tert - butylcyclohexanone ( 1.0 g , 6.49 mmol ) , 
 benzylamine 
 ( 1.0 g , 9.71 mmol ) , and dry powdered magnesium sulfate ( 4.0 g , 33.3 
 mmol ) in dichloromethane ( 10 ml ) was stirred at room temperature for 
 48 h. the reaction mixture was filtered through celite and washed 
 with water , the solvent was removed under reduced pressure , and the 
 residue was directly subjected to the next reaction without further 
 purification . to a stirred solution of the crude intermediate imine 
 in acetonitrile ( 10 ml ) were added trifluoroacetic acid ( 0.8 ml , 10.0 
 mmol ) , potassium bifluoride ( 405.0 mg , 5.19 mmol ) , and n , n - dimethylformamide ( 2.0 ml ) at 0 c . the 
 reaction mixture was stirred for 10 min and was then treated with 
 ( trifluoromethyl)trimethylsilane ( 1.4 g , 9.8 mmol ) at 0 c , and 
 the mixture was stirred at room temperature for 48 h. the reaction 
 mixture was quenched with saturated aqueous na2co3 solution ( 3 ml ) , and diluted with water ( 25.0 ml ) , and extracted 
 with ethyl acetate ( 3  100 ml ) . the combined organic layers 
 were washed with water and brine , dried over na2so4 , and evaporated under reduced pressure . the residue was dissolved 
 in meoh ( 10.0 ml ) , and the solution was stirred for 36 h with pd / c 
 ( 10 mg , 10% mol ) under 1 atm of hydrogen ( balloon ) . after completion , 
 the reaction mixture was filtered through celite , and the filtrate 
 was evaporated under reduced pressure . the residue was dissolved in 
 2 m hcl / meoh and then concentrated to dryness . the resulting hydrochloride 
 salt was crystallized from acetonitrile ( 3.0 ml ) , filtered , and washed 
 with diethyl ether to afford the hcl salts of 16ax and 16eq ( 154 mg , 68% , mp 240242 c ) in a 1:1 ratio 
 as a white solid . h nmr ( 600 mhz , cd3od ) :  
 2.37 ( d , j = 14.3 hz , 2h ) , 2.06 ( d , j = 12.8 hz , 2h ) , 1.951.83 ( m , 6h ) , 1.75 ( t , j = 13.5 hz , 2h ) , 1.401.27 ( m , 4h ) , 1.16 ( m , 2h ) , 0.92 ( s , 
 9h ) , 0.88 ( s , 8h ) ; c nmr ( 150 mhz , cd3od ) : 
  125.5 ( q , jcf = 284.9 
 hz , cf3 ) , 125.2 ( q , jcf = 282.2 hz , cf3 ) , 58.4 ( q , jcf = 25.8 hz , c1 ) , 57.2 ( q , jcf = 28.0 hz , c1 ) , 
 46.5 , 45.5 , 31.7 , 31.6 , 29.6 , 27.6 , 26.3 , 26.2 , 22.0 , 20.3 ; f nmr ( 564 mhz , cd3od ) :  73.4 ( s , cf3 ) , 80.8 ( s , cf3 ) ; fdcs ( 150 mhz , cd3od ) :  125.3 ( tt , j = 10.4 , 3.4 hz ) , 
 124.9 ( br s ) ; esihrms calcd for c11h21nf3 ( [ m + h ] ) , 224.1626 ; found , 224.1629 . to a stirred solution 
 of ( pentafluoroethyl)trimethylsilane ( 507 mg , 2.6 mmol ) in tetrahydrofuran 
 ( 1.5 ml ) were added 4-tert - butylcyclohexan-1-one 
 ( 136 mg , 0.88 mmol ) and tetrabutylammonium fluoride ( 0.26 ml , 0.26 
 mmol , 1.0 m tetrahydrofuran ) at room temperature . after 2 h of stirring , 
 6 m hcl ( 1 ml ) was added , and the reaction mixture was stirred for 
 1 h at room temperature . the aqueous layer was separated and extracted 
 with diethyl ether ( 3  3.0 ml ) . the combined organic layers 
 were washed with saturated aqueous nahco3 ( 10.0 ml ) and 
 brine ( 10.0 ml ) and dried over mgso4 . the crude products 
 were purified by flash column chromatography ( gradient elution with n - pentane / diethyl ether = 98:2 , 96:4 , 94:6 , 92:8 ) to give 
 a white solid 17ax ( 116 mg , 54% ; mp 74 c ) as the 
 major isomer and a colorless oil 17eq ( 54 mg , 25% ) as 
 the minor isomer . neither 17ax nor 17eq was 
 amenable to ionization by either electrospray or electron impact mass 
 spectrometry . 17ax : h nmr ( 600 mhz , 
 cdcl3 ) :  2.372.30 ( m , 2h ) , 2.26 ( br s , 1h , 
 oh ) , 1.731.66 ( m , 2h ) , 1.48 ( td , j = 13.8 , 4.2 hz , 2h ) , 1.35 ( tdd , j = 14.3 , 
 8.3 , 2.8 hz , 2h ) , 1.171.09 ( m , 1h ) , 0.84 ( s , 9h ) ; c nmr ( 150 mhz , cdcl3 ) :  119.4 ( qt , jcf = 280 hz , jcf = 31.9 hz , cf3cf2 ) , 116.3 ( tq , jcf = 260 hz , jcf = 28.4 hz , cf3cf2 ) , 72.2 ( t , jcf = 22.7 hz , c1 ) , 46.0 , 34.0 , 32.3 , 27.4 , 
 22.8 ; f nmr ( 564 mhz ) :  81.4 ( s , 3f , cf3cf2 ) , 121.9 ( s , 2f , cf3cf2 ) ; fdcs ( 150 mhz , cdcl3 ) :  116.3 [ qtt , j = 28.4 hz ( from 
 fluorine ) , 7.3 hz ( from axial hydrogen ) , 3.3 hz ( from equatorial hydrogen ) ] . 17eq : h nmr ( 600 mhz , cdcl3 ) :  1.911.85 ( m , 2h ) , 1.76 ( s , 1h , oh ) , 1.711.59 ( m , 4h ) , 1.38 ( m , 2h ) , 1.00 ( tt , j = 12.4 , 3.1 hz , 1h ) , 0.86 ( s , 9h ) ; c nmr ( 150 mhz , 
 cdcl3 ) :  119.5 ( qt , jcf = 288.0 hz , jcf = 31.9 hz , cf3cf2 ) , 114.8 
 ( tq , jcf = 258.0 hz , jcf = 33.4 hz , cf3cf2 ) , 73.2 ( t , jcf = 22.7 hz , c1 ) , 47.0 , 32.3 , 30.3 , 27.3 , 
 21.1 ; f nmr ( 564 mhz ) :  80.9 ( s , 3f , cf3cf2 ) , 129.5 ( s , 2f , cf3cf2 ) ; fdcs ( 150 mhz , cdcl3 ) :  119.5 broad quartet [ j = 33.4 
 hz ( from fluorine ) ] . a solution of 11ax ( 350 mg , 0.66 mmol ) in tetrahydrofuran ( 3.0 ml ) was treated with 
 2 n hcl ( 0.6 ml ) and stirred for 5 h at room temperature . the solvent 
 was evaporated under reduced pressure , and the residue was dissolved 
 in ethyl acetate ( 5.0 ml ) , washed with saturated aqueous nahco3 solution ( 5.0 ml ) and water ( 5.0 ml ) followed by brine ( 5.0 
 ml ) , dried over na2so4 , and concentrated under 
 reduced pressure afford the 3-(trifluoromethyl)-3-cholestanol , which was taken forward to the next reaction 
 without further purification . a suspension of 3-(trifluoromethyl)-3-cholestanol 
 ( 135 mg , 0.29 mmol ) and potassium hydride ( 24 mg , 0.60 mmol ) in tetrahydrofuran 
 ( 6.0 ml ) was stirred for 10 min at room temperature followed by addition 
 of carbon disulfide ( 115 mg , 1.47 mmol ) and then methyl iodide ( 420 
 mg , 2.95 mmol ) at 65 c . the resulting reaction mixture was stirred 
 for 1 h at 65 c , cooled to 0 c , and quenched with water 
 ( 5.0 ml ) . after extraction into dichloromethane ( 2  8 ml ) , the 
 combined organic layers were washed with water ( 10.0 ml ) followed 
 by brine ( 10.0 ml ) and dried over na2so4 . the 
 solvent was evaporated under reduced pressure , and the residue was 
 purified by silica gel column chromatography eluting with hexanes 
 to give 18 ( 119 mg , 74% , mp 95.596.0 c ) 
 as a white solid . [ ]d25 = + 25.4 ( c= 0.7 , dichloromethane ) ; h nmr ( 600 mhz , cdcl3 ) :  3.34 ( dt , j = 14.3 , 5.5 hz , 1h ) , 3.14 ( t , j = 14.3 
 hz , 1h ) , 2.45 ( s , 3h ) , 1.99 ( td , j = 14.3 , 2.2 hz , 
 1h ) , 1.95 ( td , j = 12.8 , 3.3 hz , 1h ) , 1.831.75 
 ( m , 2h ) , 1.71 ( dd , j = 13.5 , 4.4 hz , 1h ) , 1.66 ( m , 
 1h ) , 1.571.40 ( m , 5h ) , 1.381.18 ( m , 9h ) , 1.161.00 
 ( m , 6h ) , 1.000.93 ( m , 5h ) , 0.88 ( d , j = 6.6 
 hz , 3h ) , 0.85 ( d , j = 2.9 hz , 3h ) , 0.84 ( d , j = 2.9 hz , 3h ) , 0.69 ( dt , j = 12.5 , 4.0 
 hz , 1h ) , 0.64 ( s , 3h ) ; c nmr ( 150 mhz , cdcl3 ) :  211.4 , 125.7 ( q , jcf = 286.7 hz , cf3 ) , 91.6 ( q , jcf = 27.5 hz , c3 ) , 56.3 , 56.2 , 53.5 , 42.5 , 
 42.5 , 39.8 , 39.4 , 36.1 , 35.7 , 35.4 , 35.3 , 35.1 , 31.7 , 28.8 , 28.5 , 
 28.2 , 27.9 , 24.1 , 23.8 , 22.8 , 22.5 , 22.4 , 21.2 , 19.0 , 18.6 , 12.6 , 
 12.1 ; f nmr ( 564 mhz , cdcl3 ) :  76.7 
 ( s , cf3 ) . to a stirred 
 solution of xanthate 18 ( 102 mg , 0.18 mmol ) in allyltributyltin 
 ( 433.0 mg , 1.30 mmol ) was added triethylborane ( 20.0 mg , 0.20 mmol ) 
 at 30 c . the resulting reaction mixture was stirred 
 for 1 h at 30 c , quenched with diisopropyl azodicarboxylate 
 ( diad ) ( 452.0 mg , 2.23 mmol ) , and stirred for 3 h at room temperature . column chromatography of the reaction mixture ( silica gel , pentane ) 
 afforded a mixture of 19ax and 19eq along 
 with allyltributyltin . the residue was dissolved in anhydrous dichloromethane 
 ( 2.0 ml ) , and propionaldehyde ( 84 mg , 1.44 mmol ) was added . the reaction 
 mixture was cooled to 0 c , and boron trifluoride diethyl etherate 
 ( 205 mg , 1.44 mmol ) was added ; the resulting reaction mixture was 
 stirred at 0 c for 1 h , quenched with saturated aqueous nahco3 solution ( 2.0 ml ) , and washed with water ( 2.0 ml ) and brine 
 ( 2.0 ml ) . the solvent was evaporated under reduced pressure , and the 
 residue was purified by silica gel column chromatography eluting with 
 hexanes to obtain a mixture of 19ax and 19eq ( 49.2 mg , 55% , mp 5152 c ) in a 1:2.5 ratio as a white 
 solid . [ ]d25 = + 16.4 ( c= 2.2 , dichloromethane ) ; h nmr ( 600 mhz , cdcl3 ) :  5.71 ( m , 2h ) , 5.11 ( dd , j = 10.3 , 2.2 hz , 1h ) , 5.07 ( dd , j = 13.9 , 
 1.8 hz , 1h ) , 2.37 ( d , j = 7.3 hz , 2h ) , 2.16 ( m , 1h ) , 
 1.96 ( m , 2h ) , 1.81 ( m , 2h ) , 1.72 ( dd , j = 13.9 , 4.4 
 hz , 1h ) , 1.67 ( m , 2h ) , 1.621.41 ( m , 11h ) , 1.401.17 
 ( m , 17h ) , 1.171.03 ( m , 9h ) , 1.030.94 ( m , 4h ) , 0.910.88 
 ( m , 7h ) , 0.880.85 ( m , 8h ) , 0.79 ( s , 3h ) , 0.660.63 
 ( m , 4h ) ; c nmr ( 150 mhz , cdcl3 ) :  133.7 , 
 132.8 , 129.8 ( q , jcf = 286.1 
 hz , cf3 ) , 129.3 ( q , jcf = 283.3 hz , cf3 ) , 111.8 , 117.7 , 56.5 , 56.4 , 56.3 , 
 56.2 , 54.3 , 54.0 , 42.5 , 41.0 , 40.1 , 39.9 , 39.5 , 36.1 , 35.8 , 35.5 , 
 35.5 , 35.4 , 34.9 , 34.6 , 32.9 , 31.9 , 31.7 , 30.0 , 29.2 , 28.5 , 28.2 , 
 28.0 , 27.4 , 25.2 , 24.1 , 23.8 , 23.4 , 22.8 , 22.5 , 20.9 , 18.6 , 13.7 , 
 12.0 , 11.7 , 8.7 ; f nmr ( 564 mhz , cdcl3 ) :  
 73.1 ( s , cf3 ) , 79.3 ( s , cf3 ) ; 
 fdcs ( 150 mhz , cdcl3 ) :  19eq , 128.5 
 ( narrow multiplet ) , 19ax , 129.0 ( broad multiplet ) .