Diisopinocampheylborane, preparation

Diisopinocampheylborane. Prepared from a-pinene, this optically active and hindered reagent is of use for the conversion of f>t.s-olefins and ketones into optically active alcohols and for the resolution of olefin racemates. ... 

Method B 100 mmol of diisopinocampheylborane, prepared as above, are suspended in 50 mL of Et20 at 0SC, and hydrogen chloride gas is passed through the solution until all of the solid dissolves. Removal of the solvent provides the reagent as a white powder mp54-55cC. 

Methylcyclopentene added to ca. 0.5 mole of diisopinocampheylborane prepared by adding a soln. of BF3 in diglyme to a mixture of a-pinene and NaBH4 in the same medium, and kept 4 hrs. at 0-5° ( —)-3-methylcyclopentene. Y ... 

Monoisopinocampheylborane [64234-27-17, IpcBH2 (6) is an important asymmetric hydroborating agent. It is prepared from a-pinene (7) either directiy or better by indirect methods. The product obtained by hydroboration of a-pinene [80-56-8] is an equiUbrium mixture. Optically pure monoisopinocampheylborane is best prepared from a-pinene via diisopinocampheylborane [1091-56-1] IPC2BH (8) (64,65). Both enantiomers are readily available. 

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

To a stirred — 78 C solution of 5.85 mL (62.5 mmol) of 3-methoxy-l-prnpene in 25 mL of THf- are added 43.1 mL (50 mmol) of 1.16 M. vcc-butyllithium in cyclohexane over a 20-25 min period. The mixture is stirred at — 78 °C for an additional 10 min, and diisopinocampheyl(methoxy)borane [50 mmol prepared from (+ )-a-pinene] in 50 mL of THF is added. This mixture is stirred for 1 h, then 8.17 mL (66.5 mmol) of boron trifluoride diethyl etherate complex are added dropwise to give a solution of diisopiuocampheyl[(Z)-3-inethoxy-2-propenyl]borane. Immediately. 2.8 mL (50 mmol) of acetaldehyde are added and the mixture is stirred for 3 h at — 78 rC and then allowed to warm to r.t. All volatile components are removed in vacuo, then the residue is dissolved in pentane. The insoluble fraction is washed with additional pentane. The combined pentane extracts are cooled to 0 JC and treated with 3.0 mL (50 mmol) of ethanolamine. The mixture is stirred for 2 h at 0rC and is then seeded with a crystal of the diisopinocampheylborane-ethanolaminc complex. The resulting crystals arc filtered and washed with cold pentane. The filtrate is carefully distilled yield 5.6 g (57%) d.r. (synjanti) >99 1 (2/ ,37 )-isomer 90% ee bp 119-120 C/745 Torr. 

Cyclohexenyl(diisopinocampheyl)borane (2), prepared by the hydroboration of 1,3-cy-clohexadiene with diisopinocampheylborane, reacts with acetaldehyde at — 78 "C to provide l-(2-cyclohexenyl)ethanol in 66% yield and 94% ee21. Reactions with other aldehydes, however. have not yet been reported. 

Use of the reagent diisopinocampheylborane SO (prepared by treating optically active a-pinene with BH3) results in enantioselective hydroboration-oxidation. ° Since both (-I-) and (-) a-pinene are readily available, both enantiomers can be prepared. Alcohols with optical purities as high as 98% have been obtained in this... 

Z)- and (E)-Crotyldiisopinocampheylboranes, Ipc2BCH2CH=CHCH, (1). Brown and Bhat1 have prepared the two (Z)-crotyldiisopinocampheylboranes [derived from (-)- and (+ )-pinene] by reaction of (Z)-crotylpotassium with the methoxy-diisopinocampheylboranes. The (E)-crotyldiisopinocampheylboranes are prepared in the same way from (E)-crotylpotassium. 

Transformation of ketones to alcohols has been accomplished by many hydrides and complex hydrides by lithium aluminum hydride [55], by magnesium aluminum hydride [89], by lithium tris tert-butoxy)aluminum hydride [575], by dichloroalane prepared from lithium aluminum hydride and aluminum chloride [816], by lithium borohydride [750], by lithium triethylboro-hydride [100], by sodium borohydride [751,817], by sodium trimethoxyborohy-dride [99], by tetrabutylammonium borohydride [771] and cyanoborohydride [757], by chiral diisopinocampheylborane (yields 72-78%, optical purity 13-37%) [575], by dibutyl- and diphenylstannane [114], tributylstanrume [756] and others Procedure 21, p. 209). 

Use of the reagent diisopinocampheylborane 46 (prepared by treating optically active a-pinene with BH3) results in enantioselective hydroboration-oxidation.371 Alcohols with op-... 

This sequence has now been used to obtain optically pure aldehydes by preparation of optically active boronic esters from diisopinocampheylborane or mono-isopinocampheylborane.2 Example ... 

An alternative method of hydroboration is to use diisopinocampheylborane (12) (Scheme 4). This reaction is particularly useful for sterically hindered alkenes. Diisopinocampheylborane (12) is prepared from borane-dimethyl sulfide and (+)-pinene.[23-24] Treatment of 4-meth-ylenecyclohexanone ethylene ketal with diisopinocampheylborane (12) gives the borane 13.[25] Further treatment with 2 equivalents of an aldehyde results in the elimination of pinene and the formation of a new dialkyl boronate, e.g. treatment of 13 with acetaldehyde gives the diethyl cyclohexylmethylboronate 14J261 The dialkyl boronates thus produced can be transesterified with pinanediol to give 15[26] or with other cyclic diols. 

Diisopinocampheylborane (12) was prepared according to the method of Brown et all27 BH3-DMS (5.5 mL, 55 mmol) was dissolved in anhyd THF (20 mL) and was cooled to 0°C. a-Pinene (17.3 g, 20.2 mL, 127 mmol) was added and the mixture was stirred at 0 °C for 60 min. During this time, the white precipitate of diisopinocampheylborane formed. 4-Methylenecyclohexanone ethylene ketal (8.5 g, 55 mmol) was dissolved in THF (5mL) and was added dropwise.1251 The reaction was allowed to stir at 0°C for lh yielding a clear soln. Anhyd acetaldehyde (8.8 g, 200 mmol) was added dropwise and the reaction stirred at rt for 36 h. The solvent and a-pinene were removed by concentration and pinanediol (8.5 g, 50 mmol) in THF (40 mL) was added. After 3h, the solvent was removed and the product was isolated by column chromatography (silica gel, EtOAc/hexane 1 5) yield 96%. 

To a stirred suspension of diisopinocampheylborane (50 mmol) (1) in tetra-hydrofuran (18 ml) is added 4.5 ml of (Z)-but-2-ene. The reaction mixture is stirred at 25 °C for 4.5 hours. The solid diisopinocampheylborane disappears and the formation of the trialkylborane is complete. The organoborane is treated with 4 ml of methanol, followed by 18.3 ml of 3 m sodium hydroxide and the careful addition of 20 ml of 30 per cent hydrogen peroxide, maintaining the temperature of the reaction below 40 °C. The reaction mixture is further stirred at 55 °C for 1 hour, cooled, and extracted with ether (3 x 50 ml). The extract is washed successively with water (2 x 25 ml) and brine (3 ml) and dried over magnesium sulphate. The organic layer is carefully fractionated to provide butan-2-ol, b.p. 96-98 °C, 2.9 g (73%), purity > 95 per cent. The last traces of impurities are removed by preparative g.l.c. (2) to yield (R)-butan-2-ol, [a] 3 —13.23° (neat), ee 98.1 per cent. 

B-Pinene Is an important auxiliary for directed chiral syntheses. It has been used for preparation of mono- and diisopinocampheylborane 8-allyldiisoplnocampheylborane,6 B-pinanyl-9-bora[bicyclo]nonane, els-... 

Diisopinocampheylborane (Ipc2BH) (1), 1, 262-263 4, 161-162 6, 202 8, 174 11, 188. Two methods have been reported for preparation of either ( + )- or (-)-Ipc2BH of high optical purity from commercially available (-)- or (+ )-a-pinene of lower optical purity. Essentially pure material (99% ee) selectively crystallizes from the reaction of a-pinene with borane-dimethyl sulfide in THF-diethyl ether after storage at 0° for several hours. Somewhat purer reagent (99.9% ee) can be prepared by hydroboration of ( + )-oi-pinene (84 or 91.6% ee) with optically pure (- )-monoisocampheylborane (8, 267).1... 

Monoisopinocampheylborane [(IPC)BH2], see diisopinocampheylborane, 1, 266-268 4, 161-162. The laboratories of Pelter and of Brown have succeeded in the preparation of monoisopinocampheylborane by hydroboration of a-pinene. In one method, equimolar proportions of ( + )-a-pinene and BHs-THF are mixed in THF and the solution is allowed to stand for 96 hours, after which time it contains about 90% (IPOBH2, 4.75% (IPO2BH, and 4.75% BH3 THF. The last material is precipitated as TMEDA-2BH3, and the solution is used for hydroboration. Alternatively, addition of TMEDA precipitates TMEDA-2(IPC)BH2 as a white soiid, m.p. 139-140°. This is dissolved in THF, and then BF3 etherate is added to generate (IPOBH2. 

Kinetic resolution of vinylic epoxides by the reduction with terpenyl dialkylboranes of high optical purity is a simple and direct method for the preparation of enantiomerically enriched epoxides. It allows for convenient configurational assignment of epoxides if the configuration of the corresponding allylic alcohol is known. Both enantiomers can be prepared using readily available enantiomeric diisopinocampheylboranes. 

The new reagent 9 is efficiently prepared in three (3) steps from 1 in either enantiomeric form. Moreover use of the reagent does not necessitate temperatures lower than -78°C, and, in fact, studies indicate that the reactions may be conducted at considerably higher temperatures (i.e. 23 and 0°C) without significant loss of selectivity. This is in contrast to the behavior of the diisopinocampheylborane reagent (c.f Table 4.)16... 

A 2,5-disubstituted pyrrolidine was obtained by this method as a 1 1 mixture of cis- and tran.r-isomers. However, since diastereomeric or enantiomeric boronic esters can be easily prepared via asymmetric hydroboration, the control of the relative and absolute stereochemistry at C-2 and C-3 (ring numbering) should easily be achieved. Diisopinocampheylborane was employed in the first step, but exclusively with allyl bromide. 

Dilongifolylborane is simply prepared by admixture of borane-dimethyl sulfide and 2 equiv. (+)-lon-gifolene in THF, whereupon the product crystallizes out of solution as the dimer, and can readily be separated from the solvent. It is used as a suspension for hydroboration reactions. Diisopinocampheylborane can be prepared in a similar way from (+)- or (-)-a-pinene, and early work was carried out with reagent so prepared. However, ot-pinene is often available only in purities up to ca. 95%, so that Ipc2BH produced by direct hydroboration can also be somewhat impure. Fortunately, equilibration of the reagent (dimethyl sulfide must first be removed if borane-dimethyl sulfide is used for the hydroboration) with cn-pinene, at 0 C over several days, results in preferential incorporation of the major enantiomer of a-pinene into the Ipc2BH. This then becomes available in 98-99% enantiomeric purity. 

The use of enantiopure allylic boranes in reactions with achiral aldehydes results not only in high diastereoselection, but also in high enantioselectionP Pure (Z)- and )-crotyldiisopinocampheylboranes can be prepared at low temperature from (Z)- or E) crotylpotassium and S-methoxydiisopinocampheylborane, respectively, after treatment of the resultant ate-complexes with BF3 OEt2. The R-methoxydiisopinocampheylboranes are prepared by reacting (-)-diisopinocampheylborane, derived from (+)-a-pinene, or (+)-diisopinocampheylborane, derived from (-)-a-pinene, with methanol. 

This synthesis has been adapted to make the natural (5 -isomer of 114, reducing the initially formed aldehyde to (S)-114 with baker s yeast. [This same synthesis has been adapted to make (S)-callosobruchic acid (115), see below]. Julia s synthesis of a-geraniol (73) was also extended to make 114 by hydro-boration. Hydroboration of 73 with diisopinocampheylborane (made from (- )-a-pinene [(-)-116]) gave only a small ee however. A synthesis of ( )-114 started with the reaction of 2-methylpropiolactone and the ethylene acetal of 3-oxobutylmagnesium bromide. The methyl ester of the acid 117 thus prepared was chain-lengthened by reaction with acetylene and rearrangement with a vanadium catalyst of the ynol thereby obtained. The aldehyde 118 was then reduced with lithium aluminum hydride to 114. ... 

By hydroboration of natural products such as a-pmene, H. C. Brown and coworkers have prepared mono- 2.15 (R = H) and diisopinocampheylboranes 2.16 (R = H). These reagents promote highly enantioselective hydroborations [580, 583], The two a-pinene enantiomers are available, so both enantiomers of these reagents can be used. The intermediate di- or trialkylboranes formed in these hydroborations are treated with MeCHO. This forms a chiral boronate 2.17, and the a-pinene is freed for recovery and recycling. From 2.17, it is possible to obtain many functionalized compounds. Additionally, new chiral boranes 2.18 are available, and these are precursors of many chiral compounds bearing the R group [169, 580, 583, 585-588] (Figure 2.2). 

The dialkylchloroboranes are stronger Lewis acids and consequently reduce ketones under milder conditions than those required for the trialkylboranes. They are prepared by hydrobo-ration of an alkene to produce a dialkylborane which is then treated with hydrochloric acid. In the case of diisopinocampheylchloroborane, the intermediate diisopinocampheylborane crystallizes from solution, and the major enantiomer of a-pinene is accumulated on boron. The final borane is thus enriched to 99% ee. The boranc reagent derived from (+ )-a-pinene has a negative rotation. 

---