Reductive α-borylation of α,β-unsaturated esters using NHC–BH3 activated by I2 as a metal-free route to α-boryl esters

The combination of NHC–BH3/I2 represents a simple method for the reductive α-borylation of α,β-unsaturated esters to form useful α-boryl esters.

Mass spectrometry was attempted for the novel compounds isolated in this study, but suitable conditions to ionise the borylated species could not be found. ASAP, ESI and CI techniques were all trialled in a range of solvents, none of which were found to yield molecular ions or identifiable fragments derived from these for identification. Moreover, CHN analysis on a range of isolated borylated products resulted in unsatisfactory data therefore purity is based on the observation of clean 1 H / 11 B NMR spectral data for isolated products that fully dissolved in organic solvents. S2 2 Synthesis of Starting Materials 1,3-Dimethylimidazol-2-ylidene borane (IMe-BH 3 ) 2.1 IMe-BH 3 was synthesised using a modified version of the preparation reported by Curran et al. 1 A 2-necked round bottom flask was charged with N-methyl imidazole before DCM was added. Iodomethane was subsequently added (1.2 eq.) to the solution dropwise and the reaction was left to stir at room temperature for 2 hours. After this time the solvent was removed under vacuum, yielding an oily residue to which toluene was then added, causing the imidazolium salt to precipitate out of solution as a white solid. NaBH 4 was added (1.5 eq.) to the suspension and the mixture was heated at reflux for 18 hours, after which time the product mixture was filtered while still hot. The reaction flask was washed with further hot toluene and the washings combined before the solvent was removed in vacuo to yield the crude product as a white solid. The product was purified by recrystallization from boiling water to yield the title compound as fine white needles. The identity and purity of the product were confirmed by 1 H and 11 B NMR spectroscopy, with the data matching those previously reported in the literature. 1 IMe-BD 3 was synthesised in an identical manor, substituting NaBH 4 with NaBD 4 .

1,3-Dimethylbenzimidazol-2-ylidene borane (BenzIMe-BH 3 ) 2.2
BenzIMe-BH 3 was synthesised following a modified version of the preparation reported by Walton, Lacôte, and Curran et al. 2 A flask was loaded with N-methylbenzimidazole, before DCM was added, followed by the dropwise addition of iodomethane. The solution was left to stir at room temperature overnight before the solvent was removed under vacuum to yield a beige solid. The solid was washed with small portions of diethyl ether before drying under vacuum and dissolving in THF. The resulting solution was cooled to -78 °C before KHMDS was added, followed an hour later by the dropwise addition of BH 3 .THF. The reaction was allowed to warm to room temperature and left to stir for 16 hours, in which time a yellow solution formed along with a white precipitate. The solvent was removed under vacuum and the product was isolated by column chromatography (SiO 2 , 4:1 pet. ether/ethyl acetate). Analysis by 1 H and 11 B NMR spectroscopy confirmed the identity and purity of the title product, with the data matching those reported in the literature. 2 1,3-Diisopropylimidazol-2-ylidene borane (I i Pr-BH 3 ) 2.3 I i Pr-BH 3 was synthesised following a modified version of the preparation reported by Lacôte, and Curran et al. 1 A flask was loaded with N-isopropylimidazole before DCM was added, followed by the addition of isopropyl iodide (1.5 eq). The resulting solution was heated at reflux for 20 hours, after which time the solvent was removed under vacuum, yielding an oily residue. Diethyl ether was added and the mixture was stirred causing copious amounts of white precipitate to form. The diethyl ether was removed under vacuum before being replaced by toluene. NaBH 4 was added (0.75 eq.) and the mixture was set to reflux for 24 hours. After this time a further 0.75 eq NaBH 4 was added and the reaction was heated at reflux for another 24 hours. The toluene was removed under vacuum to yield an oily residue as the crude product. The product was purified by column chromatography (SiO 2 , 2:1 pet. ether:ethyl acetate) and the identity of the title product was confirmed by 1 H and 11 B NMR spectroscopy, with the data matching those reported in the literature. 1 5-phenylfuran-2(5H)-one 2.4 5-phenylfuran-2(5H)-one was synthesised following the preparation reported by Chang et al. 3 The identity of the product was confirmed by 1 H NMR spectroscopy with the data matching those reported in the literature.

Menthyl cinnamate 2.5
A flask was charged with cinnamoyl chloride and DCM prior to the addition of (1R,2S,5R)-(−)menthol. The solution was cooled to 0 °C and triethylamine (2 eq.) was added. The solution was allowed to warm to room temperature and left to stir for 16 hours, after which time a large amount of white precipitate had formed. The solution was washed with 3 x HCl (1 M, aq.) before the organic fraction was dried over MgSO 4 , filtered and the solvent removed under vacuum to yield the crude product as a yellow oil. The product was purified by column chromatography (SiO 2 , 9:1 pet. ether:ethyl acetate) to yield the title compound as a clear oil. The identity and purity of the product were confirmed by 1 H and 13 C{ 1 H} NMR spectroscopic data matching those reported in the literature. 4 8-phenyl menthyl cinnamate 2.6 A preparation reported by Muñiz et al. was followed. The identity of the product was confirmed by the 1 H NMR spectroscopic data matching those reported in the literature. 5 3 Conditions screening Low concentration general procedure 3.1 A Young's NMR tube was charged with IMe-BH 3 (16.5 mg, 0.15 mmol) and a C 6 D 6 filled capillary before solvent (0.5 mL) was added. Methyl crotonate (10.6 μL, 0.1 mmol) was added to the solution and NMR spectroscopy confirmed that no reaction between the starting materials had occurred. Iodine (0.005 -0.05 mmol) was then added to the mixture causing rapid effervescence before NMR spectroscopic analysis was used to confirm the composition of the reaction mixture at "t=0" (throughout t = 0 means approx. 5 minutes after addition of the last reagent). The reaction vessel was then set to mix at room temperature for 48 hours after which time the progress of the reaction was investigated by further NMR spectroscopy. Mesitylene (13.9 μL, 0.1 mmol) was added, before 1 H NMR spectroscopy was used to analyse the in situ reaction yield (measured by integration of product signals relative to mesitylene).
High concentration procedure 3.2 A Young's NMR tube was charged with IMe-BH 3 (66 mg, 0.6 mmol) and a C 6 D 6 filled capillary before CHCl 3 (0.5 mL) was added. Methyl crotonate (53 μL, 0.5 mmol) was added to the solution. Iodine (12.7 mg, 0.05 mmol) was then added to the mixture causing rapid effervescence before NMR S4 spectroscopic analysis was used to confirm the composition of the reaction mixture at t=0. The reaction vessel was then set to mix at room temperature for 20 hours after which time the progress of the reaction was investigated by NMR spectroscopy. Mesitylene (69 μL, 0.5 mmol) was added, and 1 H NMR spectroscopy used to analyse the in situ reaction yield (measured by integration of product signals relative to mesitylene). There was measured to be 70 % formation of 2a, with 95 % consumption of methyl crotonate.

4.1
A Young's NMR tube was charged with IMe-BH 3 (66 mg, 0.6 mmol) and a C 6 D 6 filled capillary before CHCl 3 (0.5 mL) was added. Methyl crotonate (53 μL, 0.5 mmol) was added to the solution. Tris(pentafluorophenyl)borane (25.6 mg, 0.05 mmol) was then added to the mixture causing some minor effervescence * before NMR spectroscopic analysis was used to confirm the composition of the reaction mixture at t=0. The reaction vessel was then set to mix at room temperature for 20 hours after which time the progress of the reaction was investigated by further NMR spectroscopy. Mesitylene (69 μL, 0.5 mmol) was added, and NMR spectroscopy used to analyse the in situ reaction yield (measured by integration of product signals relative to mesitylene in the 1 H spectrum). There was measured to be 16 % formation of 2a, with 40 % consumption of methyl crotonate.

4.2
The conditions used were analogous to the recent report on radical mediated alkyne transhydroboration by Curran et al. 6 A Young's NMR tube was charged with IMe-BH 3 (66 mg, 0.6 mmol) and C 6 D 6 (0.5 mL) was added. Methyl crotonate (53 μL, 0.5 mmol) was added to the solution. Tert-butylhydroperoxide (18 μL, 0.1 mmol, 5.5 M in nonanes) was added prior to the reaction mixture being heated at 60 °C for 18 hours. The reaction was analysed by NMR spectroscopy, showing that no conversion to the reductive borylation product had occurred (see Fig. S75 and S76). Based upon this finding no further investigation using radical initiators was carried out.

5.1
A Young's NMR tube was charged with BenzIMe-BH 3 (96 mg, 0.6 mmol) and a C 6 D 6 filled capillary before CHCl 3 (0.5 mL) was added. Methyl crotonate (53 μL, 0.5 mmol) was added to the solution. Iodine (12.7 mg, 0.05 mmol) was then added to the mixture causing rapid effervescence before NMR spectroscopic analysis was used to confirm the composition of the reaction mixture at t=0. The reaction vessel was then set to mix at room temperature for 20 hours after which time the progress of the reaction was investigated by further NMR spectroscopy. Mesitylene (69 μL, 0.5 mmol) was added, and 1 H NMR spectroscopy used to analyse the in situ reaction yield (measured by integration of product signals relative to mesitylene). There was measured to be 34 % formation of Benz-IMe-BH 2 -ester 4a, with 50 % consumption of methyl crotonate.

S5
I i Pr-BH 3

5.2
A Young's NMR tube was charged with IPr-BH 3 (100 mg, 0.6 mmol) and a C 6 D 6 filled capillary before CHCl 3 (0.5 mL) was added. Methyl crotonate (53 μL, 0.5 mmol) was added to the solution and NMR spectroscopy confirmed that no reaction between the starting materials had occurred. Iodine (12.7 mg, 0.05 mmol) was then added to the mixture causing rapid effervescence before NMR spectroscopic analysis was used to confirm the composition of the reaction mixture at t=0. The reaction vessel was then set to mix at room temperature for 20 hours after which time the progress of the reaction was investigated by further NMR spectroscopy. Mesitylene (69 μL, 0.5 mmol) was added, and 1 H NMR spectroscopy used to analyse the in situ reaction yield (measured by integration of product signals relative to mesitylene). There was measured to be 43 % formation of IPr-BH 2 -ester 3a, with 72 % consumption of methyl crotonate.
6 Larger scale synthesis of borylated esters: Larger scale synthesis of IMe-BH 2 -ester 2a 6.1 A Schlenk flask was charged with IMe-BH 3 (1.00 g, 9.1 mmol) and placed under an N 2 atmosphere before CHCl 3 (7.5 mL) was added. Methyl crotonate (0.80 mL, 7.6 mmol) was added to the flask and the resulting reaction solution was cooled to 0 °C. Iodine (192 mg, 0.76 mmol) was added to the mixture causing instant effervescence and the reaction was allowed to warm to room temperature. After being left to stir for 24 hours the solvent was removed under vacuum, yielding the crude product as an oily solid. The product was subsequently purified by column chromatography (SiO, 9:1 ethyl acetate:pet. ether) to yield 897 mg of a white crystalline solid (56 % yield). The identity and purity of the title compound was confirmed by 1 H, 13 C{ 1 H} and 11 B NMR spectroscopy. Crystals suitable for X-ray crystallography were successfully grown by slow evaporation from a chloroform solution confirming the molecular structure. Large scale synthesis of IMe-BH 2 -Phester 2k 6.2 A Schlenk flask was charged with IMe-BH 3 (1.32 g, 12 mmol) and methyl cinnamate (1.62 g, 10 mmol) before placing under an N 2 atmosphere. CHCl 3 (10 mL) was added and the resulting solution was cooled to 0 °C. Iodine (506 mg, 2 mmol) was added causing instant effervescence and the reaction was allowed to warm to room temperature. The mixture was left to stir for 20 hours, after which time the solvent was removed under vacuum to yield a pale yellow oil as the crude product. The product was purified by column chromatography (SiO 2 , 2:1 ethyl acetate:pet. ether), yielding 1.01 g of a clear colourless oil (37 % yield). The identity of the product was confirmed as the title compound by 1  An oven dried J. Young's NMR tube was equipped with a d 6 -benzene filled capillary and charged with IMe-BH 3 (0.6 mmol) before placing under an N 2 atmosphere. Chloroform (0.5 mL) was added, followed by the desired α,β-unsaturated ester (0.5 mmol). The resulting starting material solution was analysed by 1 H, 11 B and 11 B{ 1 H} NMR spectroscopy to provide a comparison for reaction monitoring. Solid I 2 (0.05 or 0.1 mmol) was added to the reaction mixture causing major effervescence in the tube, and 1 H, 11 B and 11 B{ 1 H} NMR spectra were recorded at t=0. Subsequently, the reaction was set to mix for 20 hours, after which time further NMR spectroscopic analysis was undertaken. Mesitylene (0.5 mmol) was added to the sample, and 1 H NMR spectroscopy allowed for the in situ reaction yield to be measured by integration of the product signals relative to mesitylene. A Young's ampule was charged with menthyl cinnamate (286 mg, 1 mmol) and IMe-BH 3 (132 mg, 1.2 mmol) before placing under an N 2 atmosphere. CHCl 3 (1 mL) was added and the resulting solution was cooled to 0 °C prior to addition of iodine (51 mg, 0.2 mmol). Effervescence was observed and the solution was allowed to warm to room temperature before being left to stir for 20 hours. The solvent was removed under vacuum giving an oily white residue which was purified by column chromatography (SiO 2 , ethyl acetate:pet. ether 1:1 2:1 varying polarity). Two diastereomeric products were isolated (total yield 191 mg, 48 %. Major: 108 mg, Minor: 83 mg, 57:43 d.r.). The identity of the products as that of the title compounds was confirmed by 1 H, 13 C{ 1 H} and 11 B NMR spectroscopy. Crystals of the major diastereomer suitable for X-ray diffraction were successfully grown by evaporation of a DCM solution confirming the molecular structure of the compound, and allowing for the assignment of the stereochemistry at the C-B bond as the R configuration.     Synthesis of IMe-BH 2 -8-phenyl-menthyl-ester 2t 7.4 A Young's ampule was charged with 8-phenyl-menthyl cinnamate (362 mg, 1 mmol) and IMe-BH 3 (132 mg, 1.2 mmol) before placing under an N 2 atmosphere. CHCl 3 (1 mL) was added and the resulting solution was cooled to 0 °C prior to addition of iodine (51 mg, 0.2 mmol). Effervescence was observed and the solution was allowed to warm to room temperature before being left to stir for 20 hours. Subsequently, mesitylene (139 μL, 1 mmol) was added and an aliquot of the reaction was removed and subjected to NMR spectroscopic analysis to determine the degree of substrate consumption. This indicated a combined conversion of 72 %. The sample was returned to the bulk solution before the solvent was removed under vacuum to yield the crude product mixture as an oily white residue. Two diastereomeric products were isolated by column chromatography (SiO 2 , ethyl acetate:pet. ether 1:1 2:1 varying polarity) as 167 mg and 26 mg (41 % total yield, 87:13 d.r.). The identities of the products were confirmed by 1 H, 13 C{ 1 H} and 11 B NMR spectroscopy. Crystals of the minor diastereomer were successfully crystallised from slow cooling of a hot hexane solution confirming the structure of the product, and allowing for the assignment of the stereochemistry of the C-B bond as the S configuration for the minor component, confirming the major is the R configuration at the C-B      Intermediacy of NHC-BH 2 I and the absence of any observable ester-BH 2 (NHC) adduct 8.2 The in-situ NMR spectra of IMe-BH 3 / I 2 / methyl crotonate provided the following 11 B NMR spectra at short reaction times (as stated above t=0 is approx. 5 minutes). It is apparent that a mixture of IMe-BH 3 and IMe-BH 2 I has formed and persists on addition of the ester (effectively identical spectra are observed at t=0 for all the esters studied). This indicates that iodide is more coordinating towards boron in these compounds than these esters. ; the reaction mixture ~5 minutes after the addition of I 2 (middle); the reaction mixture after mixing at room temperature for 15 hours (top).

IMe-BH 3 + Me-crotonate
Notably, on addition of N,N-Et 2 -crotonamide to mixtures of NHCBH 3 /NHCBH 2 I the iodide is displaced from boron and a new 11 B resonance is observed. On mixing for 20 hours only a trace borylated amide product is observed by 11  Due to the formation of a new compound at ca. -10 ppm in the 11 B NMR spectra with both amides the stoichiometric reaction between NHCBH 2 I and N,N-Et 2 -crotonamide was performed to probe the identity further. The spectra are shown below. This clearly shows conversion to a new product as indicated by the major signal at -9.8 ppm in the 11 B NMR spectrum. The persistence of the two vinylic protons (that are correlated in the COSY) indicates that the boron enolate is not formed, but instead it is the adduct between the amide and IMe-BH 2 . Attempts to isolate this compound or obtain mass spec were not successful in our hands. Furthermore, attempts to improve the conversion to the reductive a borylated product using different quantities of I 2 or IMeBH 3 failed to give any significantly improved results.
IMe-BH 3 + N,N-diethyl crotonamide + 10 mol % I 2 , t=0 t=20h S13 Figure   IMe-BH 3 + 0.5 eq. I 2 + N,N-diethyl crotonamide, t=0 t=20h 1 eq. IMe-BH 3 + 0.5 eq. I 2 + 1 eq. N,N-diethyl crotonamide, t=0 t=20h IMe-BH 3 / IMe-BD 3 comparison with Me-crotonate 8.4 Two identical reactions were set up following the general catalysis protocol, one containing IMe-BH 3 and the other IMe-BD 3 for comparison. Both reactions were analysed by NMR spectroscopy at a number of time points in order to observe the progress of the reaction. Both reactions were found to be effectively identical (for ratio of product : starting NHC-BH 3 complex), hence the kinetic isotope effect (KIE) is close to 1, indicting B-H cleavage is not occurring in the rate limiting step. To determine if any intermolecular steps were involved in the reductive alpha-borylation mechanism, the feasibility of a crossover reaction was tested. However, due to rapid H/D scrambling no definitive evidence could be extracted.
A Young's ampule was charged with IMe-BD 3 (136 mg, 1.2 mmol) and BenzIMe-BH 3 (192 mg, 1.2 mmol) and placed under an N 2 atmosphere. CHCl 3 (2 mL) was added, followed by methyl crotonate (211 μL, 2 mmol). The reaction mixture was cooled to 0 °C prior to addition of iodine (50 mg, 0.2 mmol). The reaction was allowed to warm to room temperature and left to stir for 48 hours. The solvent was subsequently removed under vacuum to yield the crude product mixture as an oily residue. The products were purified by column chromatography (SiO 2 , pet ether:ethyl acetate, vary from 3:2 to 1:4 respectively), yielding IMe-BH/D-ester (114 mg, 27 % yield relative to Me-crotonate) and BenzIMe-BH/D-ester (97 mg, 19 % yield relative to Me-crotonate). Extensive H/D scrambling was observed with both compounds displaying almost identical 11 B and 2 D NMR spectra containing multiple isotopomers. The identity of IMe-BH/D-ester 2a was confirmed by 1 H NMR spectroscopic data matching those previously measured (see section 6.1 for the characterisation). The identity of BenzIMe-BH/D-ester 4a was confirmed by 1 H, 13 C{ 1 H} and 11 B NMR spectroscopy. Attempts at mass spectrometry yielded no detection of the product. Crystals of compound 4a were successfully grown by slow evaporation of a chloroform solution confirming the molecular structure.  IMe-BD 2 -lactone synthesis (d 3 -2i) 8.6 A Young's ampule was charged with IMe-BD 3 (137 mg, 1.2 mmol) and placed under an N 2 atmosphere. CHCl 3 (1 mL) was added, followed by furanone (71 μL, 1 mmol) before the mixture was cooled to 0 °C. Iodine (25 mg, 0.1 mmol) was added causing rapid effervescence, after which the solution was allowed to warm to room temperature and left to stir for 24 hours. The solvent was then removed under vacuum to yield a crude product as an oily residue. The product was purified by column chromatography (SiO 2 , 95:5 DCM:MeOH) to yield the product (78 mg, 40 % yield). The identity of the product was confirmed as that of the title compound by 1 H, 13 C and 11 B NMR spectroscopy. Crystals of compound d 3 -2i suitable for X-ray diffraction studies were grown by slow evaporation from a chloroform solution, and the resulting structure was used as an input to determine predicted H-H coupling constants via the Karplus and Altona methods (see below).

S18
Assignment of stereochemistry of d 3 -2i by measuring 3 J HH coupling constant 8.7 The stereochemistry of d 3 -2i was determined by a comparison of measured and calculated 3 J HH .
The energy of the 3D structure of the protio-analogue of d 3 -2i, shown in Figure S11, was minimized from several starting positions using the MM2 minimization function of Chem3D (Version 16.0.1.4, PerkinElmer Informatics, Inc.), using default parameters, until a minimum steric energy was achieved. The resulting 3D structure was exported in MOL format then opened using MSpin (Version 2.3.2-694, MestReLab Research S. L.). The JCoupling module in MSpin was used to calculate 3JHH using the Karplus equation. 9 Equivalent J HD values were calculated using the relationship J HD = γD J HH / γH where γD and γH are the gyromagnetic ratios of deuterium and protium respectively and are given in Table S2. MSpin was also used to calculate 3 J HH using the 'Altona' method of Haasnoot, de Leeuw and Altona 10 which includes a correction for electronegativity of the substituents. The atom coordinates from the structure as determined by X ray crystallography were also passed in mol format into the JCoupling module in MSpin and values for J HH calculated using Karplus and Altona methods. These values for J HH , along with the equivalent J HD , are given in Table S3.
The majority of signals in the 1 H NMR spectrum of d 3 -2i that contain coupling constants informative for stereochemistry determination are broadened significantly due to interactions with both 2 H and 11/10 B. To overcome the broad signals and extract coupling constants we implemented an 11 Bdecoupled variant of the PSYCHE-2DJ experiment. 11 It was hoped that this would allow measurement of both the 3 J 12 and 3 J 13 coupling constants. However, J HD -which was calculated to have a magnitude of either 0.3 Hz or 1.1 Hz -was not observed and a comparison of the calculated values with only the measured value for J HH was used to determine the stereochemistry.
For the energy minimized structure, the couplings calculated using the Karplus equation, when H2 is deuterium and H3 is protium, were 3 J 12 = 0.3 Hz and 3 J 13 = 7.1 Hz. Using the Altona method 3 J 12 = 0.2 Hz and 3 J 13 = 9.7 Hz. When H2 is protium and H3 is deuterium, the Karplus equations yielded 3 J 12 = 1.8 Hz and 3 J 13 = 1.1 Hz and the Altona method gave 3 J 12 = 1.1 Hz and 3 J 13 = 1.5 Hz. A slight discrepancy in the values of the calculated and measured values (measured 3 J 13 = 8.2 Hz) for 3 J HH arises due to poor parameterisation of the electronegativity of the BH 2 -substituent in the Altona model implemented in MSpin. The Altona method applied to the structure determined by X ray crystallography gives values slightly closer to the measured value of JHH than when applied to the structure determined by computational energy minimisation. However, the Karplus method gave slightly worse agreement with experiment for the structure determined by X ray crystallography.

S28
In situ Synthesis of IMe-BCl 2 -ester from 2k 9.3 A Young's ampule was charged with a sample of IMe-BH 2 -ester 2k (58 mg, 0.21 mmol) and placed under an N 2 atmosphere. DCM (4 mL) was added, followed by N-chlorosuccinimide (59 mg, 0.43 mmol). The solution was stirred for 10 minutes after which time an aliquot of the reaction was taken for analysis by NMR spectroscopy, demonstrating clean conversion in both 1 H and 11 B NMR spectra based on comparison with similar RBCl 2 (NHC) compounds reported by Curran et al. 12 Subsequently, unpurified pinacol (26 mg, 0.21 mmol) and Et 3 N (209 µL, 1.50 mmol) were added and the solution was mixed. NMR spectroscopic analysis after 18 hours at room temperature showed no reaction. However, heating at 60 o C for 18 hours displayed complete decomposition of the product. An identical method to that used for the reduction of 2a with LiAlH 4 was used with 2a (42 mg, 0.2 mmol) and DIBAL-H (1M in hexanes, 0.4 mL, 0.4 mmol) in place of LiAlH 4 . The identity of the product was confirmed by the 1 H and 11 B NMR spectra matching those reported above for IMe-BH 2alcohol 8.
Reduction of IMe-BH 2 -ester 2k with LiAlH 4 9.6 A Schlenk flask was charged with 2k (544 mg, 2 mmol) and placed under an atmosphere of N 2 . Diethyl ether (5 mL) was added, while in a separate flask a suspension of LiAlH 4 (152 mg, 4 mmol) in diethyl ether (5 mL) was prepared. Both mixtures were cooled to -78 °C before the LiAlH 4 suspension was added slowly to the ester solution. The solution was subsequently allowed to warm to room temperature and left stirring for 16 hours. The remaining LiAlH 4 was quenched by careful addition of saturated aqueous sodium potassium tartrate solution (20 mL total). The aqueous fraction was washed with diethyl ether (3 x 20 mL) before the organic fractions were combined, dried over MgSO 4 and filtered. The solvent was removed under vacuum to yield a crude product as a colourless oil. 11 B NMR spectroscopy revealed that the crude mixture contained the desired alcohol 9 product, and an unknown by-product ( ~15 % by 11 B NMR).
Thus in this case DIBAL-H is the preferred reagent (see below) which reacts without the side product formation.  A Schlenk flask was charged with IMe-BH 2 -Ph ester 2k (272mg, 1 mmol) and placed under an N 2 atmosphere, before adding diethyl ether (3 mL). The solution was cooled to -78 °C before DIBAL-H solution (1 M in hexanes, 2.2 mL, 2.2 mmol) was added dropwise. The reaction was left to stir at -78 °C for 3 hours before being removed from the cold bath and aqueous sodium potassium tartrate (2 mL sat. solution) added while cold. The mixture was left to warm to room temperature before more sodium potassium tartrate solution (15 mL) was added. The aqueous phase was washed with diethyl ether (3 x 10 mL) and the organic fractions were combined, dried over MgSO 4 , filtered and the solvent removed under vacuum. The product 9 was isolated as a clear oil (220 mg, 90 % yield) which was characterised as the title compound by 1 H, 13 C{ 1 H} and 11 B NMR spectroscopy.

S32
Pinacol protection of IMe-BH 2 -alcohol 8 9.8 A Young's ampule was charged with IMe-BH 2 -alcohol 8 (80 mg, 0.44 mmol) and placed under an atmosphere of N 2 . Toluene (1 mL) was added, followed by pinacol (104 mg, 0.88 mmol). The resulting solution was cooled to 0 °C before adding N-chlorosuccinimide (118 mg, 0.88 mmol). The mixture was allowed to warm to room temperature and stirred for 16 hours. The toluene solution was removed from the flask, and the flask was washed with pentane (3 x 5 mL). The organic fractions were combined and the solvent removed under vacuum to yield a clear colourless oil. Analysis of the oil by 11 B NMR spectroscopy revealed two signals (34.1 ppm, 22.5 ppm). All attempts to isolate a single product from the mixture yielded increasing proportions of protodeborylation products. The 1 H NMR was consistent with the desired product by comparison to the previously reported compound.
Pinacol protection of IMe-BH 2 -Phalcohol 9 9.9 A sample of 9 (244 mg, 1 mmol) was placed in a Schlenk flask and placed under an N 2 atmosphere and pinacol (236 mg, 2 mmol) added. The solids were dissolved in toluene (5 mL) before adding N-chloro-succinimide (267 mg, 2 mmol) and stirring for 2 hours. The toluene solution was removed from the flask which was subsequently washed with pentane (3 x 5 mL). The organic fractions were combined and the solvent removed under vacuum. The oily residue was passed through a silica plug, eluting two fractions, first with pet. ether:ethyl acetate (10:1) followed by a second eluted with neat ethyl acetate. The solvent was removed from both fractions yielding two clear oils. The first pet. ether fraction was analysed by NMR spectroscopy and found to contain primarily a mixture of 11 and 12 (139 mg, 51 % yield) which were assigned based on previously reported data for both compounds. 13 The second neat ethyl fraction was found to be primarily Phalcohol-BPin 10 (81 mg, 31 % yield) which was characterised by its 1 H NMR spectrum matching that previously reported by Hoveyda et al. 15 S33 9.9.1 By-products 11 and 12  The enantiomeric excess (97%) was determined using HPLC analysis (Chiracel OD-H, Hexane : IPA 98:2, flow rate = 1.5 mL/min, 20 o C, 220 nm). The references for the racemic mixture and the authentic (S)-enantiomer of 3-phenylpropane-1,2-diol were prepared by reduction with LiAlH 4 of (rac)-3-Phenyllactic acid and (S)-3-Phenyllactic lactic, respectively.    All calculations were conducted at the M06-2X/6-311G(d,p) level with a solvation model (PCM, CH 2 Cl 2 ) using the Gaussian software package. 16 All geometry optimizations were full, with no restrictions. In all cases, structures were confirmed as minima by frequency analysis and the absence of imaginary frequencies.
Full  Crystallographic data for compound IMe-BH 2 -ester 2a were recorded on an SAXI (Bruker) diffractometer, at 150 K with Cu Kα radiation (mirror monochromator, λ =1.54184). Crystallographic data for compound BenzIMe-BH 2 -ester 4a were recorded on an Agilent Supernova diffractometer, at 150 K with Mo Kα radiation (mirror monochromator, λ =0.7107). Crystallographic data for compounds IMe-BF 2 -ester 6, IMe-BH 2 -lactone 2i, IMe-BH 2 -menthyl ester 2s and IMe-BH 2 -8-phenyl menthyl ester 2t were collected on a Rigaku FRX diffractometer with Cu Kα radiation (graphite monochromator, λ =1.54184) at 150 K. The CrysAlisPro 17 software package was used for data collection, cell refinement and data reduction. All further data processing was undertaking within the Olex2 software. 18 The molecular structures were solved with ShelXT 19 structure solution program using Intrinsic Phasing. The model was refined with the SHELXL 20-22 refinement package using Least Squares minimisation against F 2 . Non-hydrogen atoms were refined anisotropically, while hydrogen atoms were all located in a difference map and repositioned geometrically. For compound IMe-BH 2lactone 2i the lactone-ring hydrogens were freely refined, while the remaining hydrogens were located in a difference map and repositioned geometrically.