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Org. Synth. 2011, 88, 87-101
DOI: 10.15227/orgsyn.088.0087
SYNTHESIS OF (+)-B-ALLYLDIISOPINOCAMPHEYLBORANE AND ITS REACTION WITH ALDEHYDES
Submitted by Huikai Sun and William R. Roush1 .
Checked by David Hughes2
1. Procedure
A. (+)-B-allyldiisopinocampheylborane ((+)-(Ipc)2B(allyl) or (lIpc)2B(allyl)) ( 1). A 500-mL, 3-necked oven-dried round-bottomed flask equipped with a 3-cm oval Teflon-coated magnetic stir bar is fitted with a gas inlet adapter connected to a nitrogen line and a gas bubbler. The other two necks are capped with rubber septa; a thermocouple probe is inserted through one of the septa. (Note 1) The flask is charged with (+)-B-methoxydiisopinocampheylborane ((+)-(Ipc)2BOMe) (13.3 g, 42.1 mmol, 1.25 equiv) (Note 2) and diethyl ether (45 mL), which results in a clear and colorless solution. The solution is cooled to 3 °C in an ice/water bath and vigorously stirred. Allylmagnesium bromide solution (1.0 M in diethyl ether, 40 mL, 40 mmol, 1.20 equiv) (Notes 2 and 3) is then added dropwise over 20 min via a 60 mL disposable syringe with 18-gauge needle, maintaining the temperature below 6 °C. A large amount of white solids (presumably MgBr(OMe)) precipitate during the addition. After the addition is complete, the ice/water bath is removed, then the reaction mixture is vigorously stirred (Note 4) for 1 h at room temperature. The resulting (lIpc)2B(allyl) mixture in ether is used immediately in the next step without further purification (Note 5).
B. (2R,3R)-1-(tert-Butyldiphenylsilyloxy)-2-methylhex-5-en-3-ol (3). The heterogeneous mixture of (lIpc)2B(allyl) generated in Step A is cooled to -75 °C with a dry ice/acetone bath under vigorous stirring, then a solution of (R)-3-(tert-butyldiphenylsilyloxy)-2-methylpropanal (2) (10.9 g, 33.4 mmol, 1.00 equiv) (Note 6) in diethyl ether (25 mL) is added dropwise over 20 min via syringe (Note 7), maintaining the temperature below -70 °C. The resulting mixture is vigorously stirred at -70 to -75 °C for 1.5 h (Note 8), then the dry ice/acetone bath is removed, and the reaction mixture is allowed to warm to room temperature (22 °C) over 1 h. The reaction mixture is cooled to 3 °C with an ice/water bath. A 125-mL gas equilibrating dropping funnel is attached to the flask, moving the gas adapter from one neck of the flask to the top of the dropping funnel. A premixed solution of 3M NaOH (64 mL) and 30 % H2O2 (26 mL) (Note 9) is carefully added via the dropping funnel over 10 min (exothermic), keeping the temperature below 15 °C, followed by addition of saturated aqueous NaHCO3 (80 mL) over 3 min via the dropping funnel (Note 10). The resulting biphasic mixture is vigorously stirred for 10 h at room temperature (Note 11) to completely hydrolyze borinate ester products, then the organic phase is separated, and the aqueous phase is extracted with diethyl ether (2 × 80 mL). After the combined organic layers are washed with brine (2 × 50 mL), the ether solution is transferred to a 1-L round-bottomed flask, equipped with a 3-cm, egg-shaped Teflon-coated stir bar, then THF (150 mL), water (80 mL) and iron (II) sulfate heptahydrate salt (15.0 g) are added (Note 12). The flask is fitted with a gas inlet adapter connected to a nitrogen line and a gas bubbler. The resulting mixture is vigorously stirred for 14 h, then the organic phase is separated and the aqueous phase is extracted with diethyl ether (2 × 50 mL). The combined organic layers are washed with brine (2 × 50 mL), dried over 100 g of anhydrous Na2SO4 and vacuum filtered through a medium porosity sintered-glass funnel. The filtrate is concentrated (40 °C bath temperature, 100 mmHg initial to 20 mmHg) by rotary evaporation to give a light yellow residue (32 g), containing a 93 : 7 mixture of 3 and its anti diastereomer (5) (Note 13). This mixture is purified by column chromatography (Note 14) to provide 9.1 - 9.4 g (74 - 77%) of >98% pure (2R,3R)-1-(tert-butyldiphenylsilyloxy)-2-methylhex-5-en-3-ol 3 (Note 15) as a colorless oil.
2. Notes
1. The internal temperature was monitored using a J-Kem Gemini digital thermometer with a Teflon-coated T-Type thermocouple probe (12-inch length, 1/8 inch outer diameter, temperature range -200 to +250 °C).
2. (+)-B-Methoxydiisopinocampheylborane was purchased from Sigma-Aldrich and used as received. The submitters stored and transferred this material in the glove box. The checker stored it in the freezer and weighed and transferred (rapidly) in open air. Diethyl ether (anhydrous, ACS reagent) and allylmagnesium bromide (1.0 M in diethyl ether, stored in refrigerator) were purchased from Sigma-Aldrich and used as received.
3. The specified amounts of (+)-(Ipc)2BOMe (1.25 equiv) and allylmagnesium bromide (1.20 equiv) are used in order to generate a sufficient amount of allylborane 1 to completely consume 1.0 equiv of aldehyde 2 in the allylboration step. Unreacted aldehyde (8-10%) remains at the end of the allylboration reaction when 1.0 equiv of both (+)-(Ipc)2BOMe and allylmagnesium bromide are used. A slight excess of (+)-(Ipc)2BOMe is used over allylmagnesium bromide in order to ensure complete consumption of the latter before addition of the aldehyde; the submitters observed that the allylboration diastereoselectivity decreased by 1-2% if a slight excess of (+)-(Ipc)2BOMe is not used.
4. The stirring of the thick mixture should be vigorous but balanced. Solids that stick on the walls above the mixture may contain entrapped reagent, perhaps in the form of the ate complex indicated in equation 1,3 and cannot be washed back into the reaction mixture. In such cases, unreacted aldehyde is often observed after conclusion of the allylboration reaction.
5. (-)-B-allyldiisopinocampheylborane ((-)-(Ipc)2B(allyl) or (dIpc)2B(allyl)), can be prepared using the same procedure starting from (-)-B-methoxydiisopinocampheylborane ((-)-(Ipc)2BOMe). The (Ipc)2B(allyl) reagents are sensitive to air and moisture.
6. (R)-3-(t-Butyldiphenylsilyloxy)-2-methylpropanal 2 was prepared (10.0 - 12.0 g scale) according to the procedure of Marshall et al.4 and obtained in 75-80% yield as a white solid following column chromatography with 3% EtOAc/hexanes with [α]D 20 -26.4 (CHCl3, c = 1.8). Aldehyde 2 was stored at -20 °C for up to 2 weeks prior to use without racemization (as determined by measuring its optical rotation and ee determination of the allylation product 3).
7. An oven-dried, 100-mL, single-necked, round-bottomed flask was charged with (R)-3-(t-butyldiphenylsilyloxy)-2-methylpropanal 2 (10.9 g), then 25 mL of diethyl ether was added, and the mixture was swirled to completely dissolve the aldehyde. The resulting solution was transferred to the reaction mixture via a 40 mL disposable syringe with a 15 cm needle (18 gauge) over 20 min. Additional diethyl ether (2 × 5 mL) was used to rinse the flask and then was added to the reaction mixture over 1 min. For the addition of the aldehyde solution to the cold reaction mixture, the tip of the syringe needle should be kept >5 cm above the surface and added at a steady rate to prevent crystallization of the aldehyde in the syringe. The submitters used a syringe pump for this addition.
8. The progress of the reaction was monitored by 1H NMR spectroscopy monitoring the aldehyde proton at δ 9.8. (Typical procedure for 1H NMR analysis: an aliquot of the reaction mixture was quickly transferred via a syringe to a small vial containing methanol (0.5 mL) at rt. The solvent was evaporated and the residue was dissolved in CDCl3.)
9. 30% H2O2 was purchased from Fisher Chemical Company, stored at 5 °C and used as received.
10. The oxidative hydrolysis was not complete in 16 h at ambient temperature or under reflux without addition of the saturated NaHCO3 solution. The pH of the hydrolysis reaction mixture after bicarbonate addition was 11.
11. The progress of the oxidative hydrolysis was monitored by 1H NMR pdf spectroscopy using CDCl3 as solvent (An aliquot of the organic layer was evaporated to dryness and the residue dissolved in CDCl3.) Completion of the oxidative hydrolysis was indicated by disappearance of the mutiplet resonances of the internal olefin hydrogen (δ 5.78 - 5.68) and terminal olefin hydrogens (δ 5.05 - 4.95) in the intermediate borinate ester (e.g., ROBIpc2). In comparison, the chemical shift range of the multiplet of the corresponding olefinic hydrogens in the major product 3 are from δ 5.92 - 5.81 and 5.16 - 5.09. The hydrolysis was complete within 1.5 h in the hands of the submitters but typically required 8-10 h for the checkers. Agitation efficiency of the 3-phase mixture (aqueous, organic, solids) may affect the reaction rate.
12. Isopinocampheyl hydroperoxide 4 is produced in the reaction. This compound migrates with the syn product 3 on the TLC plate (EMD, silica gel, grade 60, F254) in this exemplified allylboration reaction, so the iron (II) sulfate reduction step is included to ensure that hydroperoxide 4 is completely consumed prior to product isolation. A reference sample of 4 was prepared by stirring a solution of Ipc2BOMe (1.0 g) in THF under air for 1 h. This solution was cooled to 0 °C and a premixed solution of 3 N NaOH (2.3 mL) and 30% H2O2 (0.9 mL) was added followed by sat. NaHCO3 (3.0 mL) solution. The resulting mixture was vigorously stirred for 1.5 h. The organic phase was separated and hydroperoxide 4 was separated from isopinocampheol (1 : 4 mixture, respectively) by column chromatography using 1:10 Et2O-hexanes as eluent (Rf=0.5, 1:5 Et2O-hexanes, staining with PMA).
13. The reaction diastereoselectivity was determined as follows. A small sample of the crude reaction product (80 mg) was purified (collecting all fractions containing product with Rf = 0.4 to 0.5) by flash column chromatography (8 g silica gel) using ether/hexanes = 1/8 as the eluent to provide a mixture of three products. This mixture was analyzed by the submitters using normal phase HPLC (5% EtOAc in hexanes, 1.0 mL/min, 4.6 × 250 mm Varian column, UV detection at 254 nm; tR(3) = 16.2 min; tR(5) = 13.9 min; tR(6) = 13.0 min). The checkers used a reverse phase assay to analyze diastereomeric ratios using an Agilent 1100 HPLC system; Ascentis Express C-18 fused-core column, 4.6 × 100 mm, 2.7 um particle size; 1.8 mL/min flow; temperature 40 °C; detection at 210 nm; gradient elution from 50/50 MeCN/water containing 0.1% H3PO4 to 95% MeCN/5% aq. over 14 min; tR (3) 9.6 min, tR (5) 9.8 min, tR (6) 11.6 min). The crude reaction product was determined to contain (2R,3R)-1-(t-butyldiphenylsilyloxy-2-methylhex-5-en-3-ol (3) (90%), (2R,3S)-1-(t-butyldiphenylsilyloxy)-2-methylhex-5-en-3-ol (5) (7%), and (2R, 3R)-1-(t-butyldiphenylsilyloxy)-2-methyl-5-methyleneoct-7-en-3-ol (6) (3%). The stereochemistry of the hydroxyl group of 6 is assumed, by analogy to the stereochemistry of the major product of the reaction (3). A use test (by direct reaction with aldehyde 2) indicated that the solutions of allylmagnesium bromide in diethyl ether contain ca. 3% of 2-((bromomagnesium)methyl)-1,4-pentadiene.
14. The crude product was purified by three flash column chromatography steps owing to the difficulty of separating the syn diastereomer 3 from the anti diastereomer 5 and the byproduct 6. The first chromatography was performed using 300 g of silica gel (Fisher, 230-400 mesh, 60 Å) in a 5 cm diameter column using 10:1 hexanes-diethyl ether as the eluent (18-mL fractions). All fractions were analyzed by TLC (1:10 Et2O-hexanes, 3 developments, staining with KMnO4 solution), as depicted
graphically below. Early fractions contained 0.7 g of a mixture of 5 and predominantly by-product 6. Late eluting fractions without detectable anti diastereomer 5 were pooled, giving 3.7 g of syn diastereomer 3. The intermediate fractions, containing 8.1 g of a mixture of 3, 5 and 6 were pooled and subjected to a second chromatography as described above (250 g silica gel, 5 cm diameter column). Early eluting fractions containing predominantly 5, 6 and a small amount of 3 were discarded. Late eluting fractions, without detectable anti diastereomer 5 according to TLC analysis, were combined to give an additional 3.4 g of syn diastereomer 3. The intermediate, mixed fractions, consisting of 4.5 g of a mixture of 3, 5 and 6 were subjected to a third column chromatography (200 g of silica gel in a 5 cm diameter column). This provided an additional 2.3 g of essentially pure syn diastereomer 3, along with 1.5 g (12% yield) of mixed fractions that consisted of mixture 3 (ca. 80%), 4 (ca. 20%) and 6 (ca. 1 %). The latter fraction could be subjected to additional purification if desired. The three main fractions of syn diastereomer 3 were combined, giving 9.4 g (77% yield) which contained 1.3% of anti diastereomer 5 and 0.2% of by-product 6 according to HPLC analysis as described in note 13.
15. The submitters obtained pure samples of 3, 5 and 6 by preparative HPLC for spectroscopic analysis (5% EtOAc in hexanes, 18.0 mL/min, 21.4 × 250 mm Varian Dynamax column, Microsorb 60-8; tR(3) = 9.8 min; tR(5) = 9.1 min; tR(6) = 8.3 min). The enantiomers of both 3 and 5 have been synthesized and characterized previously.5 The checker prepared a mixture of the (2S, 3S) and (2S, 3R) diastereomers by the same protocol starting with (S)-3-(t-butyldiphenylsilyloxy)-2-methylpropanal and (+)-B-methoxydiisopinocampheylborane, which produced a 78:22 mixture of (2S, 3R):(2S, 3S) diastereomers. The syn product 3 exhibits the following physical and spectroscopic properties: colorless oil; [α]D 21 = +3.7 (c = 1.9, CHCl3); 1H NMR pdf (400 MHz, CDCl3) δ: 0.97 (d, J = 7.1 Hz, 3 H), 1.08 (s, 9 H), 1.77-1.82 (m, 1 H), 2.20-2.33 (m, 2 H), 2.73 (d, J = 3.4 Hz, 1 H), 3.70 and 3.77 (ABX, J = 10.1, 4.3 Hz, 2 H), 3.92-3.97 (m, 1 H), 5.09-5.16 (m, 2 H), 5.81-5.92 (m, 1 H), 7.30-7.48 (m, 6 H), 7.67-7.71 (m, 4 H); 13C NMR pdf (125 MHz, CDCl3) δ: 10.5, 19.4, 27.1, 39.1, 39.3, 68.7, 73.5, 117.3, 128.0, 130.00, 130.04, 133.2, 133.4, 135.79, 135.81, 135.9; IR (KBr) 3468, 2955, 2858, 1606, 1515, 1471, 1427, 1112, 701 cm−1; LC-MS calcd for [M+Na]+ (C23H32NaO2Si) 391.6, found, 391.7 m/z. Purity by reverse phase HPLC was >98% (see note 13 for method), tR (3) 9.6 min (98.3%); tR (5) 9.8 min (1.3%); tR (6) 11.6 min (0.2%); tR 9.1 min (unknown, 0.2%). A reverse phase chiral HPLC assay was developed to separate the (2S, 3S) and (2R, 3R) enantiomers: OJ-RH (150 × 4.6mm, 5um) isocratic 60% MeCN (pH 3.5, 2mM ammonium formate), 40% aqueous (pH 3.5, 2mM ammonium formate), 0.75mL/min, ambient temp, 215 nm, 20 min method time; tR(3) (2R, 3R) 11.5 min; tR (2S, 3S) 13.2 min; tR (5) (2R, 3S) and (2S, 3R) co-elute 12.5 min. The enantiomeric purity of 3 was 99.0% indicating that aldehyde 2 did not racemize during its preparation and application in the exemplified procedure. An analytical sample of 3 was prepared by dissolving ~100 mg of the product from the pooled chromatographies in 5 mL of diethyl ether, filtering through a 0.45 micron PTFE syringe filter, and concentrating to dryness under vacuum for 16 h. Anal. calcd. for C23H32O2Si: C, 74.95; H, 8.75; found: C, 74.85; H, 8.78. The anti product 5 exhibits the following physical and spectroscopic properties: colorless oil; [α]D 21 = -2.6 (c = 0.7, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 0.85 (d, J = 6.8 Hz, 3 H), 1.06 (s, 9 H), 1.80-1.84 (m, 1 H), 2.17-2.23 (m, 1 H), 2.34-2.39 (m, 1 H), 3.49 (d, J = 3.2 Hz, 1 H), 3.65 and 3.77 (ABX, J = 10.0, 4.4 Hz, 2 H), 3.65-3.73 (m, 1 H), 5.10-5.15 (m, 2 H), 5.88-5.98 (m, 1 H), 7.38-7.45 (m, 6 H), 7.67-7.69 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ: 13.4, 19.1, 26.8, 39.4, 39.5, 68.6, 75.1, 117.2, 127.8, 129.8, 132.9, 135.3, 135.6, 135.7; IR (KBr) 3496, 2959, 2930, 2858, 1589, 1472, 1427, 1390, 1112, 701 cm−1; LC-MS calcd for [M+Na]+ (C23H32NaO2Si) 391.6, found, 391.7 m/z. The side product 6 exhibits the following physical and spectroscopic properties: colorless oil; 1H NMR (400 MHz, CDCl3) δ: 0.93 (d, J = 6.8 Hz, 3 H), 1.07 (s, 9 H), 1.76-1.80 (m, 1 H), 2.20-2.28 (m, 2 H), 2.49 (d, J = 3.6 Hz, 1 H), 2.82 (d, J = 6.8 Hz, 2 H), 3.68 and 3.73 (ABX, J = 10.4, 4.8 Hz, 2 H), 4.04-4.07 (m, 1 H), 4.90 (d, J = 0.8 Hz, 2 H), 5.05-5.10 (m, 2 H), 5.78-5.88 (m, 1 H), 7.38-7.46 (m, 6 H), 7.66-7.70 (m, 4 H); 13C NMR (100 MHz, CDCl3) δ: 10.4, 19.2, 26.9, 39.3, 40.6, 41.1, 68.0, 70.8, 112.9, 116.5, 127.7, 129.7, 129.8, 133.1, 133.3, 135.6, 135.7, 136.1, 145.3; IR (KBr) 3400, 2928, 2859, 1607, 1515, 1470, 1463, 1455, 1112, 822, 702, 505 cm−1; LC-MS calcd for [M+Na]+ (C26H36NaO2Si) 431.6, found, 431.6 m/z. Isopinocampheyl hydroperoxide 4 exhibits the following physical and spectroscopic properties: colorless oil; [α]D 21 = + 33.2 (c = 0.7, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 0.92 (s, 3 H), 1.01 (d, J = 9.6 Hz, 1 H), 1.17 (d, J = 7.2 Hz, 3 H), 1.22 (s, 3 H), 1.79-1.86 (m, 2 H), 1.90-1.95 (m, 1 H), 2.00-2.03 (m, 1 H), 2.30-2.42 (m, 2 H), 4.27 (ddd, J = 3.6, 4.4 and 8.8 Hz, 1 H), 7.73 (s, 1 H); 13C NMR (100 MHz, CDCl3) δ: 1.41, 23.61, 27.30, 32.48, 33.56, 38.40, 40.87, 42.14, 47.24, 84.99; IR (KBr) 3391, 2908, 1453, 1367, 1158, 1035 cm−1; LC-MS calcd for [M-H2O]+ (C10H18O2) 152.1, found, 152 m/z. This compound is readily reduced by Fe2SO4 to give isopinocampheol.
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
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3. Discussion
Chiral allylmetal reagents are valuable intermediates in organic synthesis, and are especially useful for the synthesis of enantioenriched homoallylic alcohols.6 Since the first chiral allylborane reagent was reported by Hoffman in 1978,7 many more efficient and practical chiral allylmetal reagents or allylmetallation procedures have been reported, 6 including those by Brown,8 Roush,5,9 Corey,10 Leighton,11 Denmark,12 Soderquist,13 Hall14 and Krische.15 The present enantioselective aldehyde allylation procedure developed by Brown and his coworkers is one of the most widely adopted methods as it employs commercially available (+)-(Ipc)2BOMe and commercially available allylmagnesium bromide for synthesis of the (lIpc)2B(allyl) reagent; 8b the enantiomeric (dIpc)2B(allyl) species can be accessed from commercially available (-)-(Ipc)2BOMe by using the same protocol.
The (Ipc)2B(allyl) reagents were prepared in Brown's original procedure8b by treating (Ipc)2BOMe with allylmagnesium bromide at -78 °C and then allowing the reaction mixture to warm to rt over 1 h. The procedure described herein follows an alternative protocol subsequently published by Brown, in which allylmagnesium bromide is added to a solution of (Ipc)2BOMe in diethyl ether at 0 °C and then stirring the reaction mixture at rt for 1 h.3 The allylboration of aldehydes can be performed after removal of the magnesium salts by filtration under an inert atmosphere (salt free procedure), which is reported to provide much improved enantioselectivites.3 However, the procedure described here, by performing the allylboration in the presence of the magnesium salts, is more convenient as it avoids filtration and extra manipulations of the moisture and air sensitive allylborane species.
We found that use of slight excesses of both (Ipc)2BOMe (1.25 equiv) and allylmagnesium bromide (1.2 equiv) were needed in order to achieve complete allylboration of aldehyde 2. Generally, the secondary alcohol products can be isolated following oxidative hydrolytic workup by treating the intermediate borinate esters with a solution of 3 N sodium hydroxide and 30% hydrogen peroxide under reflux for several hours or at rt for 16 h. However, we found that the hydrolysis did not proceed to completion in the allylboration reaction reported here unless a solution of sat. sodium bicarbonate was also added. These optimized workup conditions not only resulted in complete oxidative hydrolysis in 10 h at room temperature, but also led to formation of two clear phases that facilitated the separation process. The submitters also found that isopinocampheyl hydroperoxide 4 is produced in 4-6% yield. While the origin of 4 has not been rigorously established, it seems likely that it arises via a radical process when the borinate ester intermediates are exposed to O2 during reaction workup.16 Hydroperoxide 4 is difficult to separate from syn product 3 in this exemplified reaction, so the submitters further modified the reaction workup by addition of an aqueous solution of iron (II) sulfate to reduce hydroperoxide 4 before product purification via column chromatography.17
The submitters also identified (2R, 3R)-1-(tert-butyldiphenylsilyloxy)-2-methyl-5-methyleneoct-7-en-3-ol (6, 3% according to HPLC analysis) as a by-product of this procedure. A use test (by direct reaction with aldehyde 2) indicated that the solutions of allylmagnesium bromide in diethyl ether contains ca. 3% of 2-((bromomagnesium)methyl)-1,4-pentadiene. Production of analogous products deriving from 2-((bromomagnesium)methyl)-1,4-pentadiene as a contaminant of allylmagnesium bromide have not been described in the literature, to the best of the knowledge of the submitters. Whether the formation of this by-product can be avoided by using freshly prepared allylmagnesium bromide has not been determined.
Reactions of (Ipc)2B(allyl) reagents with achiral aldehydes are reported to furnish the corresponding secondary homoallylic alcohols with 80 to 95% enantiomeric excess, as shown in Table 1. The substrate scope has been extended in the literature to a large number of aliphatic aldehydes, aromatic aldehydes and α, β-unsaturated aldehydes.6f
Table 1. Allylboration of achiral aldehydes with (dIpc)2B(allyl) or (lIpc)2B(allyl)
Table 1. Allylboration of achiral aldehydes with (dIpc)2B(allyl) or (lIpc)2B(allyl)
Allylboration of α-chiral aldehydes with (Ipc)2B(allyl) reagents are also reported to produce secondary homoallylic alcohols in excellent diastereoselectivity and in good to excellent yields as shown in Table 2.8c,19 In most cases (entries 1-3), with aldehyde substrates with very modest diastereofacial biases, the facial selectivity of the reaction is completely reversed upon switching the chirality of the chiral allylborane reagents. Numerous other applications of the use of the (Ipc)2B(allyl) reagents in matched and mismatched double asymmetric reactions with chiral aldehydes are summarized in the cited review literature.6a,6f
Table 2. Allylboration of α-chiral aldehydes with (dIpc)2B(allyl) or (lIpc)2B(allyl)
Table 2. Allylboration of α-chiral aldehydes with (dIpc)2B(allyl) or (lIpc)2B(allyl)
References and Notes
  1. Department of Chemistry, The Scripps Research Institute, Scripps Florida, 130 Scripps Way #3A2, Jupiter, FL 33458. E-mail: . This research was supported by a grant from the National Institutes of Health (GM038436).
  2. Checker is indebted for the analytical support from Kevin Maloney for the reverse-phase HPLC assay of diastereomers and Zainab Pirzada for the chiral HPLC assay.
  3. Racherla, U. S.; Brown, H. C. J. Org. Chem. 1991, 56, 401-404.
  4. Johns, B. A.; Grant, C. M.; Marshall, J. A. Org. Synth. 2002, 79, 59-71.
  5. Roush, W. R.; Hoong, L. K.; Palmer, M. A. J.; Straub, J. A.; Palkowitz, A. D. J. Org. Chem. 1990, 55, 4117-4126.
  6. (a) Roush, W. R., In Comprehensive Organic Synthesis, Trost, B. M., Ed. Pergamon Press: Oxford, 1991; Vol. 2, p 1. (b) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207. (c) Denmark, S. E.; Almstead, N. G., In Modern Carbonyl Chemistry, Otera, J., Ed. Wiley-VCH: Weinheim, 2000; p 299. (d) Chemler, S. R.; Roush, W. R., In Modern Carbonyl Chemistry, Otera, J., Ed. Wiley-VCH: Weinheim, 2000; p 403. (e) Denmark, S. E.; Fu, J. Chem. Rev. 2003, 103, 2763. (f) Lachance H.; Hall, D. G. Org. React. 2008, 73, 1.
  7. (a) Herold, T.; Hoffmann, R. W. Angew. Chem. Int. Ed. 1978, 17, 768. (b) Hoffmann, R. W.; Herold, T. Chem. Ber. 1981, 114, 375.
  8. (a) Brown, H. C.; Jadhav, P. K. J. Am. Chem. Soc. 1983, 105, 2092. (b) Jadhav, P. K.; Bhat, K. S.; Perumal, P. T.; Brown, H. C. J. Org. Chem. 1986, 51, 432. (c) Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986, 108, 5919. (d) Brown, H. C.; Jadhav, P. K.; Bhat, K. S. J. Am. Chem. Soc. 1988, 110, 1535. (e) Brown, H. C.; Bhat, K. S.; Randad, R. S. J. Org. Chem. 1989, 54, 1570. (f) Brown, H. C.; Randad, R. S.; Bhat, K. S.; Zaidlewicz, M.; Racherla, U. S. J. Am. Chem. Soc. 1990, 112, 2389.
  9. (a) Roush, W. R.; Walts, A. E.; Hoong, L. K. J. Am. Chem. Soc. 1985, 107, 8186. (b) Roush, W. R.; Banfi, L. J. Am. Chem. Soc. 1988, 110, 3979. (c) Roush, W. R.; Hoong, L. K.; Palmer, M. A. J.; Park, J. C. J. Org. Chem. 1990, 55, 4109. (d) Roush, W. R.; Ando, K.; Powers, D. B.; Palkowitz, A. D.; Halterman, R. L. J. Am. Chem. Soc. 1990, 112, 6339. (e) Roush, W. R.; Palkowitz, A. D.; Ando, K. J. Am. Chem. Soc. 1990, 112, 6348.
  10. Corey, E. J.; Yu, C. M.; Kim, S. S. J. Am. Chem. Soc. 1989, 111, 5495.
  11. (a) Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X.; Leighton, J. L. J. Am. Chem. Soc. 2002, 124, 7920. (b) Kubota, K.; Leighton, J. L. Angew. Chem. Int. Ed. 2003, 42, 946. (c) Hackman, B. M.; Lombardi, P. J.; Leighton J. L. Org. Lett. 2004, 6, 4375.
  12. (a) Denmark, S. E.; Fu, J. J. Am. Chem. Soc. 2001, 123, 9488. (b) Denmark, S. E.; Fu, J.; Lawler, M. J. J. Org. Chem. 2006, 71, 1523,
  13. (a) Burgos, C. H.; Canales, E.; Matos, K.; Soderquist, J. A. J. Am. Chem. Soc. 2005, 127, 8044. (b) Canales, E.; Prasad, K. G.; Soderquist, J. A. J. Am. Chem. Soc. 2005, 127, 11572,
  14. (a) Lachance, H.; Lu, X.; Gravel, M.; Hall, D. G. J. Am. Chem. Soc. 2003, 125, 10160. (b) Kennedy, J. W. J.; Hall, D. G. J. Org. Chem. 2004, 69, 4412. (c) Rauniyar, V.; Hall, D. G. J. Am. Chem. Soc. 2004, 126, 4518. (d) Rauniyar, V.; Hall, D. G. Angew. Chem., Int. Ed. 2006, 45, 2426. (e) Rauniyar, V.; Zhai, H.; Hall, D. G. J. Am. Chem. Soc. 2008, 130, 8481. (f) Rauniyar, V.; Hall, D. G. J. Org. Chem. 2009, 74, 4236.
  15. (a) Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 6340. (b) Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 14891. (c) Bower, J. F.; Kim, I. S.; Patman, R. L.; Krische, M. J. Angew. Chem. Int. Ed. 2009, 48, 34. (d) Kim, I. S.; Han, S. B.; Krische, M. J. J. Am. Chem. Soc. 2008, 130, 6340. (e) Kim, I. S.; Han, S. B.; Krische, M. J. Chem. Commun. 2009, 7278.
  16. Davies, G. J. Chem. Res. 2008, 7, 361.
  17. Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765.
  18. Cardona, W.; Quinones, W.; Robledo, S.; Velez, I. D.; Murga, J.; Garcia-Fortanet, J.; Carda, M.; Cardona, D.; Echeverri, F. Tetrahedron 2006, 62, 4086.
  19. Brown, H. C.; Bhat, K. S.; Randad, R. S. J. Org. Chem. 1987, 52, 319.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

(+)-B-Allyldiisopinocampheylborane ((+)-(Ipc)2B(allyl) or (lIpc)2B(allyl)); (106356-53-0)

(+)-B-Methoxydiisopinocampheylborane ((+)-(Ipc)2BOMe); (99438-28-5)

Allylmagnesium bromide; (1730-25-2)

(R)-3-(t-Butyldiphenylsilyloxy)-2-methylpropanal: Propanal, 3-[[(1,1-dimethylethyl)diphenylsilyl] oxy]-2-methyl-, (2R)-; (112897-04-8)

(R)-3-(t-Butyldiphenylsilyloxy)-2-methylpropanal: Propanal, 3-[[(1,1-dimethylethyl)diphenylsilyl] oxy]-2-methyl-, (2R)-; (112897-04-8)

Hydrogen peroxide; (7722-84-1)

(1R,2R,3R,5S)-2,6,6-Trimethylbicyclo[ 3.1.1 ]heptan-3-ol; (+)-isopinocampheol; (24041-60-9)

(2R,3R)-1-(t-Butyldiphenylsilyloxy)-2-methylhex-5-en-3-ol

(2R,3S)-1-(t-Butyldiphenylsilyloxy)-2-methylhex-5-en-3-ol

(2R,3R)-1-(t-Butyldiphenylsilyloxy)-2-methyl-5-methyleneoct-7-en-3-ol

(1S,2S,3S,5R)-3-hydroperoxy-2,6,6-trimethylbicyclo[3.1.1]heptane; (+)-isopinocampheylper oxide

William R. Roush is Professor of Chemistry, Executive Director of Medicinal Chemistry and Associate Dean of the Kellogg School of Science and Technology at The Scripps Research Institute, Florida. His research interests focus on the total synthesis of natural products and the development of new synthetic methodology. Since moving to Scripps Florida in 2005, his research program has expanded into new areas of chemical biology and medicinal chemistry. Dr. Roush was a member of the Organic Syntheses Board of Editors from 1993-2002 and was Editor of Volume 78. He currently serves on the Organic Syntheses Board of Directors (2003-present).
Huikai Sun received both his BS and MS degrees in Organic Chemistry from Nankai University in China. He joined the Department of Chemistry at Case Western Reserve University for his Ph. D. degree, which was completed in 2007 under the supervision of Professor Anthony J. Pearson. He is currently a postdoctoral research associate in the laboratory of Professor William R. Roush at Scripps Florida. His research interests focus on the total synthesis of natural products and the development of cysteine protease inhibitors.
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