In-depth structure – selectivity investigations on asymmetric, copper-catalyzed oxidative biaryl coupling in the presence of 5-cis -substituted prolinamines †

Thirteen new and 25 known prolinamines carrying an additional 5-cis substituent were evaluated as the chiral ligands in asymmetric copper-catalyzed, oxidative biaryl coupling of 3-hydroxy-2-naphthoates. Comprehensive structure – selectivity investigations revealed that a phenyl group in the 5-cis position and a small substituent at the pyrrolidine nitrogen ( e.g. , Me) are essential for high levels of chirality transfer. The sense of the asymmetric induction depends on the steric demand of the exocyclic amino function. In the coupling of methyl 2-hydroxy-3-naphthoate, a primary amino group permitted up to 36% ee in favor of the P -enantiomer, while up to 64% ee in favor of the M -enantiomer was reached with secondary and tertiary amino functions ( e.g. NMe 2 , Ĳ S )-NHCH Ĳ Me)Ph). A fully linear relationship between the enantiomeric excess of the prolinamine and the binaphthol was observed. A mechanism consistent with all stereochemical findings is proposed, indicating that 3-hydroxy-2-naphthoates with bulkier ester groups should permit better stereocontrol. Indeed, the enantiomeric excess was raised to good 87% when tert -butyl 3-hydroxy-2-naphthoate was used as the substrate.


Introduction
A chiral biaryl axis is the characteristic and dominating feature of a wide variety of bioactive natural products 1 and privileged ligands for enantioselective synthesis. 2During the past three decades, many efficient and strategically diverse methods for the stereoselective construction of chiral biaryl bonds have been developed, from the desymmetrization of achiral, but rotationally hindered biaryls and the stereochemical fixation of configurationally labile ones through the atroposelective construction of aromatic rings to diastereoand enantioselective biaryl coupling reactions. 3,4mong the latter approaches, oxidative coupling reactions of 2-naphthols 3c in the presence of chirally modified copper catalysts have received particular attention, [5][6][7] since these reactions offer a direct access to the important class of axially chiral 1,1′-binaphthol derivatives. 2A first breakthrough in this field was achieved by Nakajima et al. in 1995. 8-10 The oxidative coupling of the naphthol 1a, catalyzed by 10 mol% of a complex generated from CuCl and the prolinamine 3, provided the 1,1′-binaphthyl-2,2′-ol 2a in good 85% yield and 78% ee (Scheme 1).As for most copper-diamine catalysts developed so far, the additional ester group at C2 (or another coordinating electron-withdrawing group allowing bidentate binding) is crucial for a high level of enantioselection. 11Further seminal work was done by Kozlowski et al. introducing the C 2 -symmetric 1,5-diaza-cisdecalin 4. 12,13 The CuI complex of 4 proved to be a highly enantioselective catalyst, providing, for example, the model biaryl 2a in good 85% yield and excellent 93% ee. 12 This system was successfully applied in the total synthesis of several axially chiral biaryl natural products. 13Among all other diamines evaluated so far in the enantioselective, copper-catalyzed oxidative coupling of 1a, 14 only the CuCl complex of Ha's C 1 -symmetric BINAM Ĳ1,1′-binaphthyl-2,2′diamine) derivative 5 was able to provide binaphthol 2a in comparable 94% ee. 15 The highest level of asymmetric induction (97% ee) was recently reported by Sekar et al., using a 2 : 1 ratio of C 2 -symmetric BINAM (6) and CuCl in combination with the stable radical additive TEMPO Ĳ(2,2,6,6-tetramethylpiperidin-1-yl)oxyl). 16n the course of our investigations on conformationally rigid diamines 17 we became interested in prolinamines of general types 8-10, which possess, as compared to other proline derived ligands, an additional substituent R 1 in the 5-cis position.Upon chelation of a metal (see complex 7), this substituent R 1 should shield the upper left face, which might result in enhanced levels of stereocontrol in asymmetric synthesis.This assumption was recently corroborated by coppercatalyzed, enantioselective Henry reactions 18 of nitromethane with a series of aromatic, heteroaromatic, vinylic, and aliphatic aldehydes. 19The CuCl 2 and CuBr 2 complexes of the simple prolinamine 9a (R 1 = Ph; R 2 , R 4 = Me; R 3 = H) provided the corresponding β-nitro alcohols with 99% ee in all cases (36 examples).This successful application and the structural similarity of 8-10 to Nakajima's diamine 3 prompted us to study the performance of 8-10 in the enantioselective, copper-catalyzed oxidative biaryl coupling of 1 to 2. With the broad variety of derivatives available, in-depth investigations on structure-selectivity relationships should be possible.

Synthesis of the prolinamines
We recently developed three tailor-made routes to prolinamines of type 8-10 that all start from cheap L-pyroglutamic acid (11), but differ in the order of introduction of the substituent at the 5-cis position (R 1 ), at the pyrrolidine nitrogen atom (R 2 ), and at the exocyclic aminomethyl function (R 3 , R 4 ). 20The high flexibility and applicability of these approaches was demonstrated in the preparation of more than 25 derivatives with widely varying substitution patterns.Some of these compounds were used in this study.The new prolinamines 8a, b and 9b-l (Table 1) were all synthesized from the amino alcohol 12, which is available from 11 in seven steps and 49% overall yield 19,20 and possesses a 5-cis-phenyl substituent and an N-methyl group at the pyrrolidine.Activation of the hydroxy function of 12 by mesylation and subsequent treatment with an excess of the respective amine HNR 3 R 4 afforded the target prolinamines in one pot operations. 21Two bulky tertiary amines (8a, b), ten secondary amines (9b-k) with varying steric demand and, in part, additional stereogenic centers, and one aniline substituent (9l) were thus introduced in acceptable to good 47-78% yield.

Validation of the enantiomer analysis
Initially, an accurate determination of the enantiomeric excess of the stereochemically enriched binaphthyl 2a by HPLC on chiral phase proved to be difficult. 22Just picking a   This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.

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small sample from the product, which was obtained as a slightly yellowish solid after column chromatography, and dissolving it in the HPLC solvent led to huge derivations in the ee measured.For example, the ee-values of a scalemic sample with 63% ee varied between 27% and 80%, depending on the position the material was taken from.Thus, the solid material of 2a is not stereochemically homogeneous, but a conglomerate of areas with different enantiopurities.Furthermore, the low solubility of 2a in typical HPLC solvents such as hexane, isopropanol, ethanol, or methanol in connection with the high tendency of 2a to form racemic (micro)crystals 8b bears the risk of an exaggerated enantiomeric excess in the solution to be measured.
We solved these problems by using the following procedure for sample preparation: the complete material of 2a gathered from column chromatography was dissolved in dichloromethane (ca. 1 mL per 10 mg) giving a homogeneous, clear solution.A small aliquot was taken, evaporated, and dissolved in methanol (ca.50 μg mL −1 ) under ultra-sonification and warming.The resulting solution was directly injected into HPLC, providing reliably and reproducibly ee-values (Δee ≤ 1%) as checked by several control measurements.

Optimization of the reaction conditions
All copper-diamine complexes were freshly prepared prior to use by stirring a solution of the copper salt and the respective 5-cis-substituted prolinamine 8-10 in acetonitriledichloromethane 0.9 : 1 for 20 min.After evaporation, the residue was dissolved in the reaction solvent, providing a clear green solution.
The reaction conditions were optimized using the simple prolinamine 8c (R 1 = Ph, R 2 -R 4 = Me) as the chiral ligand (Table 2).Because of the close structural relationship of 8c with diamine 3, 8b we initially chose Nakajima's conditions (entry 1), but added mol sieves 4 Å, which is known 12a to be beneficial to the reaction rate and yield.After 72 h at 20 °C, the oxidative coupling of naphthol 1a afforded binaphthol 2a in high 91% yield and acceptable 61% ee in favor of the M-enantiomer.In agreement with the literature, 8b the enantiomeric excess of 2a was easily raised by trituration with ethyl acetate, giving highly enriched (M)-2a (96% ee) in the mother liquor.
Variation of the reaction parameters showed that chlorinated hydrocarbons and mol sieves 4 Å are essential for high yields and enantioselectivities (entries 1-6).Small changes in the relative stoichiometry CuCl/8c (1.2 : 1-0.9 : 1) had no measureable effect on the chirality transfer (entries 7 and 8).Nine mol% of the catalyst was required; lower loadings resulted in significantly reduced yields (entries 9-11).CuI was not suited as the metal salt because of the formation of side products (entries 12 and 13).CuCl 2 Ĵ2H 2 O (entry 14) and CuCl gave comparable results, as expected from the redox process CuĲI) ⇄ CuĲII) in the catalytic cycle, in which both oxidation states are involved.The enantioselectivity of the oxidative biaryl coupling can be enhanced to 75% ee by lowering the temperature from 20 °C to 0 °C (entry 16), albeit at the price of a reduced yield (65% within 72 h).At −20 °C, a drastic breakdown of the reaction rate was observed (56% yield after 7 days in the presence of 18 mol% catalyst), in combination with just a poor further gain in chirality control (77% ee, entry 17).The dilution had no significant effect on the chirality transfer, although the best results at 20 °C (91% yield, 64% ee) were obtained at higher concentration (c = 0.5 M, entry 19).As the oxidant, air can be used instead of oxygen, but the reaction rate slows somewhat down (entry 20).tBuOOH and AgCl afforded lower yields and diminished enantioselectivities, while no biaryl coupling was observed with DDQ (entries 21-23).

Structure-selectivity studies
The facile and modular access to various prolinamines of type 8-10 permitted in-depth investigations on the structure-enantioselectivity relationship.All four substituents R 1 -R 4 were separately varied and their influence on the chirality transfer was studied.
The N-methyl group at the pyrrolidine nitrogen atom is essential since all variations of R 2 (8k-m, R 2 = H, Et, Bn) led to lower enantioselectivities (15-28% ee, entries 9-11).A similar small substituent tolerance was observed for R 3 and R 4 at the exocyclic amino function (entries 12-17).Good enantioselectivities (63-64% ee) were only reached with the model diamine 8c (R 3 , R 4 = Me) and the pyrrolidine derivative 8o.Even a slight increase in the steric demand of one or both substituents at the NR 3 R 4 group as, for example, in 8q ĲNR 3 R 4 = NEt 2 ) and 8p ĲNR 3 R 4 = piperidinyl) resulted in drastically reduced enantioselectivities (6-42% ee).Finally, it should be noted that the formation of the M-atropoenantiomer of 2a was favored in all coupling reactions in the presence of a diamine 8.
In the screening of the secondary prolinamines 9 (R 3 = H), we first kept the optimized substituents R 1 = Ph and R 2 = Me and varied R 4 at the exocyclic amino group (Table 4).To our surprise and in contrast to the results with all tertiary diamines 8 (see Table 3), the P-atropoenantiomer of 2a was preferentially formed (19% ee) in the presence of 9a, which possesses the sterically least hindered secondary aminomethyl function (R 4 = Me, entry 1).Even a slight increase in the bulkiness of R 4 deteriorated the P-preference and a racemic mixture was obtained with 9b (R 4 = Et, entry 2).More demanding α-branched substituents R 4 tilted the sense of stereoinduction in favor of the M-enantiomer.A broad maximum plateau in the range of 58-61% ee was reached for R 4 = 3-pentyl, ĲS)-1-phenylethyl, ĲS)-1-phenylpropyl, and ĲS)-3,3-dimethylbutan-2-yl (9e-h, entries 5-8).The configuration of the stereocenter in the α-position in 9f-h was also of importance, as seen in the reaction with 9i, which carries, compared to 9f, the enantiomeric ĲR)-1-phenylethyl side chain, and provided (M)-2a in lower 49% ee (entry 9).A further increase in the steric demand in R 4 was not favorable.
With bulky α-tertiary substituents such as tBu (9j) and CĲCH 2 OBn) 3 (9k), the stereoinduction sharply dropped to 42% and 22% ee, respectively (entries 10 and 11).The reaction rates, which roughly correspond to the isolated yields after 72 h, also decreased with the rising steric demand of R 4 .The aniline derivative 9l failed to induce a good chirality transfer (38% ee, entry 12).Curious by the reversed stereoinduction observed with the prolinamine 9a, we wondered whether the P-preference could be raised by the appropriate choice of the substituents.Since an increase in the size of R 2 at the pyrrolidine nitrogen atom had led to a loss of chirality transfer with the M-selective prolinamines 8l and 8m (see Table 3, entries 10 and 11), we anticipated that the opposite effect, an enhanced P-selectivity, should occur with the analogous derivatives of 9a.However, just slightly higher 24% ee (vs.19% ee for 9a) was found for the N-ethyl diamine 9m, whereas the sense of stereoinduction switched back to M for 9n and 9o carrying the larger N-benzyl and N-isopropyl groups (Table 5, entries 1-3).
The structure-enantioselectivity relationships found show that there is a complex interplay between the relative and absolute steric bulk of the substituents R 1 -R 4 .Significant findings are: (i) the catalyst system is highly sensitive to steric overcrowding.In particular at the positions R 2 and R 3 , only the small substituents (R 2 = Me and R 3 = Me, H) are tolerated.(ii) The stereoselection rises with an enhanced steric demand of R 1 .This accounts for the M-selective prolinamines as well as for the P-selective ones.(iii) In the prolinamine series with R 1 = Ph and R 2 = Me (8a-c, n-q, 9a-l and 10e), the sense of stereoinduction can be steered by the size and degree of substitution of the exocyclic NR 3 R 4 group.Tertiary diamines of type 8 generally provide the M-enantiomer of 2a, but good levels of enantioselection require small substituents as in 8c and 8o ĲNR 3 R 4 = NMe 2 , pyrrolidinyl).Roughly the same chirality transfer is achieved with the secondary diamines 9e-h possessing a sterically more demanding, α-branched alkyl substituent R 4 .(iv) P-configured 2a is preferentially formed, albeit with lower stereocontrol, if an NHMe group as in 9a and 9m or a primary NH 2 group as in 10b-f is present.(v) A hydrogen bridging between the catalyst and the naphthols to be coupled can be excluded for the M-selective prolinamines since the best ligand, 8c, does not possess an acidic proton; for the P-selective ligands 9a, m and 10b-f ĲNR 3 R 4 = NH 2 ), however, such an additional prefixation might be possible.Furthermore, the screening revealed that there are significant differences between our prolinamines and the known diamines 3 8 and 4. 12 For example, both latter ligands require at least one secondary amino function for high levels of asymmetric induction, while 8c has just tertiary ones.In addition, the optimum reaction conditions elaborated for diamine 4 (CuI, solvent MeCN) gave only unsatisfying results with our prolinamine 8c (see Table 2, entries 4, 12, and 13).

Mechanistic and stereochemical considerations
Kozlowski et al. 12 did extensive studies on the mechanism of enantioselective, oxidative biaryl coupling 23 in the presence of their catalyst CuI•4, finding first order dependences on the oxygen and catalyst concentrations.12d The rate determining step of the catalytic cycle is the reoxidation of the catalyst by O 2 , 12d which presumably involves several oxygenated dimeric or oligomeric species. 24,25The stereochemically decisive formation of the biaryl axis is proposed to proceed in two consecutive steps, a face-selective coupling of two naphthyl radicals, 26 of which at least one is chelated to a tetrahedral diamine-Cu-complex, followed by a central-to-axial chirality transfer upon rearomatization.12c,27 Since the counter ion has no effect on the stereoselection, it is likely that the reaction takes place at a cationic metal complex.12b Finally, a positive nonlinear effect 28 was observed, hinting at dimeric or oligomeric catalyst species in solution.12b This assumption was furthermore corroborated by VPO measurements.12b Our mechanistic studies started with the proof that the 64% ee in the product (M)-2a, as achieved with the catalyst CuCl•8c, is based on a stereodifferentiating coupling step, and not, as observed for coupling with stoichiometric amounts of chirally modified Cu complexes, 9 on a non-stereoselective coupling followed by resolution or deracemization of the primarily formed, racemic biaryl.A mere diastereoselective crystallization of CuClĴ8cĴĲM)-2 can safely be excluded because the amount of (M)-2 isolated was by far larger than the amount of the catalyst used.A subsequent deracemization by atropodiastereomerization of configurationally unstable copper complexes, namely CuClĴ8cĴĲM/P)-2 to CuClĴ8cĴĲM)-2, can be ruled out since there was no change in the optical purity if scalemic or racemic 2a were treated with the catalyst for several days.
A fully linear relationship between the enantiomeric excess of the prolinamine 8c and the product 2a was found (Fig. 1).The absence of a nonlinear effect 28 makes the existence of dimeric or oligomeric catalyst species as well as a participation of two molecules of the catalyst in the stereochemically decisive biaryl coupling step unlikely (although both possibilities cannot fully be ruled out).
Based on the aforementioned mechanistic investigations and our studies we propose the following mechanism for the oxidative biaryl coupling of 1a in the presence of our prolinamine-derived copper catalysts (Scheme 2).For simplification of the discussion, a phenyl group in the 5-cis position (R 1 = Ph) and an N-methyl group at the pyrrolidine nitrogen atom (R 2 = Me), which are both essential for good levels of stereoselection, and a secondary or primary exocyclic amino function are set.The ligands 9e-h ĲNR 3 R 4 = NHR 4 ; Fig. 1 Fully linear relationship between the enantiomeric excess of the prolinamine 8c and the binaphthol 2a.R 4 = secondary alkyl, 58-61% ee in favor of M) and 10e ĲNR 3 R 4 = NH 2 , 36% ee in favor of P) fulfill these premises.
Taking the relative and absolute steric demands of the substituents R 1 -R 4 into account, this mechanism can be extended to all prolinamines that provided significant levels of asymmetric induction.Initial chelation of the chiral prolinamine to CuCl provides the bicyclic, C 1 -symmetric complex 13, to which the naphthol 1a principally can bind in two different orientations, as illustrated in the tetrahedral 29 complexes 14A and 14B. 30The preference for one or the other is controlled by steric factors.On the side of the naphthol 1a, the methoxy group of the ester function is more demanding than the two carbon atoms C-4 and C-4a of the aryl ring.On the side of the chiral catalyst, it is reasonable that, in the energetically most favored conformation, the larger substituents at the two nitrogen atoms (R 4 and the annelated pyrrolidine) occupy opposite positions with respect to the central copper heterocycle and align pseudo-equatorially, as the phenyl group does.As a consequence of this arrangement depicted in 13, the lower right quadrant is shielded by the phenyl group and the upper left one by R 4 (see "front view").In the case of 10e with R 4 = H, only the repulsion by the phenyl group exists, thus favoring the formation of 14B, while in the cases of 9e-h (R 4 = secondary alkyl), the higher steric demand of R 4 dominates, thus favoring the orientation shown in 14A.
The following steps are identical for both catalytic cycles.Multistage 24 and rate-limiting 12d,25 oxidation of the copperĲI) atom in 14 by O 2 affords the copperĲII) complexes 15, which can undergo electron transfer from the naphthol to the copper atom to give the naphthyl radicals 16.In both complexes, the backside of the naphthyl radical is efficiently shielded by the phenyl group, possibly supported by some π-stacking, complexation of [1a˙] to a second, chirally modified copper atom and, thus, a coupling between two molecules of 16, unlikely.
During the rearomatization process via twofold ketoenol tautomerism, the two (pre)aromatic moieties have to rotate in order to reach the orthogonal alignment in biaryls.This rotation follows the pathway of the least steric hindrance, which means that the carbonyl groups pass each other and not the aromatic rings (repulsion of the peri-H).12c,27 Consequently, the rotation is clockwise in 17A, leading to M-configuration at the newly created biaryl axis in 18A, whereas an anticlockwise rotation takes place in 17B, creating the P-configured biaryl axis in 18B.Final exchange of the binaphthol 2a against naphthol 1a completes the catalytic cycle.For the orientation of 1a upon complexation, the very same steric arguments apply as in the chelation of 1a to 13 giving 14A and 14B.
Since most of the prolinamines 8-10 used in this study favored the formation of (M)-2a, the top faces of the respective copper complexes must be more strongly shielded than the bottom faces, which forces the incoming naphthol 1a to bind in a fashion shown in 14A.This also means that the steric demand of the annelated, R 1 -substituted pyrrolidine cannot be high, probably due to its pseudo-equatorial orientation with respect to the central copper heterocycle.The size of R 1 at this ring, however, exerts a drastic effect on the level of stereoselection.Since the same trendsdecreasing the bulkiness of R 1 led to a reduced chirality transfer (see 8d-j, Table 3, and 10a-f, Table 5)were observed for the Mand the P-directing prolinamines, this substituent cannot play an important role in the binding of 1a, but must be decisive in the shielding of the backside of the complexed naphthyl radical in 16A and 16B (see Scheme 2), which is in good agreement with the mechanism proposed.

Consequences of the mechanism
Under the assumption that the backside-shielding in 16 and the central-to-axial chirality transfer occur with high selectivity, the resulting enantiomeric excess in the binaphthol 2a is thus determined by the orientation of 1a during binding to 18 (and 13 in the starting sequence).As a consequence, the enantioselection of the M-selective catalysts should increase if the steric differentiation in the naphthol substrate is more pronounced, which can be achieved by raising the steric bulk of the ester group at C-2.In order to consolidate this theory, we synthesized the naphthol esters 1b-d and subjected these compounds to the coupling procedures (Table 6).Indeed, the levels of stereoselection significantly increased by using the sterically more hindered esters.The binaphthol 2d (R = tBu) was produced in good 78% and 75% ee with the prolinamines 8c and 9f as the chiral ligands (entries 4 and 8).This trend is in sharp contrast to the observations made in other oxidative biaryl coupling reactions in the presence of diamine-copper catalysts, in which the chirality transfer dropped when the size of the ester group was increased.8b,12c,14a, 16 By lowering the reaction temperature to 0 °C, the enantiomeric excess in the CuCl•8c catalyzed coupling of 1d to 2d was further improved to 87%, without any noticeable loss in yield (96%, entry 9).The latter result is the best asymmetric induction so far reached with the naphthyl ester 1d.
For the P-selective catalyst CuCl•10e, the enantioselection achieved with the methyl ester 1a and the t-butyl ester 1d was virtually identical (entries 10 and 11).This result is also in

Conclusions
A series of 38 prolinamines 8-10, which differ in the substituents R 1 at the 5-cis position, R 2 at the pyrrolidine nitrogen atom, and R 3 R 4 at the exocyclic amino function, were evaluated in their performance as chiral ligands in the coppercatalyzed oxidative biaryl coupling of the naphthol 1a.Essential for good enantioselectivities were a 5-cis-phenyl (R 1 ) and an N-methyl group (R 2 ).With these two substituents given, the level and sense of the asymmetric induction can be steered by the NR 3 R 4 group.Good 58-64% ee in favor of the M-enantiomer of 2a were reached with the tertiary amine 8c ĲNR 3 R 4 = NMe 2 ) and the secondary amines 9e-h ĲNR 3 R 4 = NHR 4 , with R 4 = secondary alkyl), while the P-enantiomer of 2a was preferentially formed with the primary amine 10e (36% ee, NR 3 R 4 = NH 2 ).A mechanism, in which the steric demand of the NR 3 R 4 group of the chiral ligand determines the orientation of 1a upon complexation to the copper atom and, thus, the sense of the chirality transfer, was proposed.
The 5-cis-phenyl group (R 1 ) plays the decisive role in the faceselective C,C-coupling step by shielding one side of the complexed naphthyl radical.As a consequence of the structure-enantioselectivity investigations, we concluded that naphthols with bulkier ester groups should permit better stereocontrol.Indeed, the enantiomeric excess of the oxidative coupling of 1d (CO 2 R = CO 2 tBu) was improved to up to 87% ee by using CuCl•8c as the chiral catalyst.

Experimental
All reactions with moisture-sensitive reagents were carried out under an argon atmosphere in anhydrous solvents, prepared using standard procedures. 31Commercially available reagents (highest quality available) were used as received.

Table 2
Optimization of the reaction conditions for the oxidative biaryl coupling of 1a to 2a in the presence of 8c

Table 3
Oxidative biaryl coupling of 1a in the presence of the tertiary prolinamines 8

Table 4
Oxidative biaryl coupling of 1a in the presence of the secondary prolinamines 9a-l a Isolated yield.b Determined by HPLC on chiral phase.

Table 5
Oxidative biaryl coupling of 1a in the presence of the primary and secondary prolinamines 9m-o and 10a-f a Isolated yield.b Determined by HPLC on chiral phase.c Naph = 1-naphthyl.

Table 6
Oxidative biaryl coupling of 1a-d in the presence of the prolinamines 8c, 9f and 10e Determined by HPLC on chiral phase.c See Table 2, entry 19.d See Table 4, entry 6. e See Table 5, entry 8. Open Access Article.Published on 19 January 2015.Downloaded on 2/15/2019 1:54:56 AM.This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
a Isolated yield.b The enantiomeric excess of the binaphthols 2a-d was determined by HPLC analysis (Waters Alliance HPLC; Waters 2695 Separation Module, Waters 2487 Dual λ Absorbance Detector) on chiral phase (Daicel Chiralpak AD-H).
13C NMR data were performed on the basis of 2D NMR methods (COSY, HSQC, HMBC).Infrared spectra were recorded on a Jasco FT-IR-410 or a PerkinElmer Spectrum 100 FT-IR spectrometer, high resolution mass spectra on a Bruker Daltonics micrOTOF focus mass spectrometer using ESI (electronspray ionization).