Boranes diisopinocampheylborane

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... 

By reaction of borane with two equivalents of a-pinene 15, the chiral hydroboration reagent diisopinocampheylborane 16 (Ipc2BH) is formed ... 

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. 

Given this restriction, an area of uncertainty still remains. In case of the reaction of (Z)-2-butene with diisopinocampheylborane (l)6, it appears sensible to proceed as follows. If the primary diastereoisomeric boranes 2a, b are characterized, either by isolation or spectroscopy, the reaction can be classed as distereoselective but if, without characterization, oxidation to 2-butanol is performed, the reaction has to be classed as enantioselective. 

Diisopinocampheylborane, 117 followed by protonation Borane-Dimethylamine, 42 Borane-Tetrahydrofuran, 42 (R,R)- and (S,S)-/r ms-2,5-Dimethyl-borolanes, 119... 

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. 

More recently, boranes such as diisopinocampheylborane and a-iso-pinocampheyl-9-borabicyclo[3.3.1]nonane have been shown to be valuable reagents for the synthesis of chiral compounds.10 The reaction of borane with a-pinene gives diisopinocampheylborane... 

Asymmetric hydroboration.1 This borane effects enantioselective hydroboration of rr. v-trisubstituted acyclic and cyclic olefins to provide, after oxidation, (R)-alcohols with optical purities of 60 78% ee. The steric requirements of 1 are less than those of diisopinocampheylborane(l, 262-263 4, 161), but greater than those of isopinocam-phcylborane (8,267). 

Both antipodes of a-pinene are available, which upon hydroboration with borane leads to both forms of diisopinocampheylborane (IPC2BH) depicted below ... 

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... 

Related Reagents. Diisopinocampheylborane Dilongifolyl-borane Monoisopinocampheylborane. 

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. 

Diisopinocampheylborane [IPC2BH, bis(pinan-3 3-yl)borane] is a chiral reagent obtained by hydroboration of (-1-)- or (-)-a-pinene. Hydroboration of cw-alkenes with (-h) or (-)-Ipc2BH creates new chiral centers." ... 

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. 

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. 

Borane can be selectively removed from the mixture by the addition of an appropriate amount of Ar, A ,A , A -tetramethylethylenediaminc (TMEDA). The diamine/borane (1/2) adduct precipitates and can be removed. The small amount of diisopinocampheylborane present in the solution does not usually interfere in hydroborations with the more reactive monoisopinocampheylborane. However, the optical purity of the reagent does not exceed the purity of the starting a-pinene. 

In Fig. 4, reaction A is a highly stereoselective reduction of 1-aryl alkanones with (-)-chlo-ro diisopinocampheylborane [21]. Upon co-ordination of the ketone oxygen with the Lewis acidic chirotopic and non-stereogenic [22] boron atom of the chiral reagent, two diastereo-isomeric complexes arise. The sterically less hindered one is preferentially formed and leads the major (,S)-enantiomer, which is isolated after a work-up that allows recovery of a-pinene, the chiral alkene from which the borane is prepared. 

Chiral boranes can be used as reducing agents for carbonyl compounds. 30 Brown prepared a variety of chiral boranes in connection with extensive studies of hydroboration reactions (sec. 5.4.B). Reaction of diborane and a-pinene, for example, gave (-)-( / ,25,3/ ,5/ )-diisopinocampheylborane (206), which reduced carbonyl derivatives to alcohols with high asymmetric induction.33 Trialkylboranes are also capable of... 

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