Diisopinocampheylborane hydroboration

Asymmetric hydroboration. Diisopinocampheylborane (1, 262-263 4, 161) is a useful reagent for asymmetric hydroboration of disubstituted olefins, but reacts only slowly with hindered trisubstituted olefins. For such substrates, the less hindered borane 1 is a useful reagent. Thus it reacts with 1-methyIcyclo-pentene at - 25° oxidation leads to 7ronj-2-methylcyclopentanol with an optical purity of 55.4%, with the new asymmetric center having the (S)-configuration. The paper reports asymmetric hydroboration of two other alkenes. 

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... 

Asymmetric Hydroboration. Hydroboration—oxidation of (Z)-2-butene with diisopinocampheylborane was the first highly enantioselective asymmetric synthesis (496) the product was R(—)2-butanol in 87% ee. Since then several asymmetric hydroborating agents have been developed. Enantioselectivity in the hydroboration of significant classes of prochiral alkenes with representative asymmetric hydroborating agents is shown in Table 3. 

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

The synthesis of chiral a-substituted allylborane 2 via the hydroboration of 1,3-cyclohexa-diene with diisopinocampheylborane has been reported21. 

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... 

In the area of ion sensing, cation recognition by electrodes containing functionalized redox-active polymers has been an area of considerable interest. Fabre and co-workers have reported the development of a boronate-functionalized polypyrrole as a fluoride anion-responsive electroactive polymer film. The electropolymerizable polypyrrole precursor (11) (Fig. 11) was synthesized by the hydroboration reaction of l-(phenylsulfonyl)-3-vinylpyrrole with diisopinocampheylborane followed by treatment with pinacol and the deprotection of the pyrrole ring.33 The same methodology was utilized for the production of several electropolymerizable aromatic compounds (of pyrrole (12) (Fig. 11), thiophene (13 and 14) (Fig. 11), and aniline) bearing boronic acid and boronate substituents as precursors of fluoride- and/or chloride-responsive conjugated polymer.34... 

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

The stereochemical outcome of hydroboration, syn steroselectivity, was originally based on the stereochemistry of alcohols isolated after hydroboration-oxida-tion.349,350 Thus, for example, (+)-a-pinene yields (—)-isopinocampheol after the oxidation of (—)-diisopinocampheylborane (36) ... 

From alkenes by hydroboration-oxidation Diisopinocampheylborane, 117 (R,R)- and (S,S)-trans-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. 

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). 

Asymmetric hydroboration.2 Extensive studies indicate that 1 is the reagent of choice for chiral hydroboration of rrans-disubstituted alkenes and trisubstituted alkenes. The corresponding alcohols are obtained in 72-100% ee and all have the same absolute configuration. Surprisingly, this configuration is the opposite to that obtained by hydroboration with diisopinocampheylborane. 

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... 

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. 

The hydroboration of acetylenes (3) with diisopinocampheylborane (IpC)2BH in THF led after refunctionalisation and transesterification to the olefins (4a, b, c) isolated in good yields. Monooxidation with mCpBA led to the sulfoxide (4d) whereas the sulfone (4e) was obtained with two equivalents of mCpBA. The same sulfone (4e) could also be obtained in an excellent overall yield by radical addition of phenylsulfonyl iodide to the pinacol ester of vinylboronic acid followed by a dehydroiodination in the presence of Et2N (87 % overall yield). The carboxylic ester (4a) could be transformed into the corresponding carboxylic acid (4f) (79 % yield) 11 which led to the acid chloride (4g) by treatment with freshly distilled thionyl chloride at 0°C (91 % yield), p-keto vinylboronates are easily accessible by oxidation of the corresponding protected allylic alcohol according to the following scheme ... 

Diisopinocampheylborane is usually used for the hydroboration of relatively unhindered, disubstituted Z-alkenes. Optical purities of the product alcohols are high (Table 2) while the absolute configuration is consistently the same for similar structures. Models predicting the product configuration in the hydroboration of alkenes with mono- and diisopinocampheylborane have been proposed54-59. The preferred transition state structure for the reaction of (Z)-2-butene with ( — )-diisopinocampheylborane is shown in Section D.2.5.2.1.3. 

The ability of diisopinocampheylborane to hydroborate Z-alkencs with a high level of asymmetric induction has been used in the synthesis of natural products, e.g., loganin60, prostaglandins61,62 and carotenoids63. Deuterated alcohols have been obtained by the deu-teroboration of terminal and internal alkenes or by the hydroboration of deuterated alkenes55,56-64-66. 

Monoisopinocampheylborane (method A) has a lower steric requirement than diisopinocampheylborane (method C). This feature makes it well suited for reactions with more hindered alkenes. Thus, the two reagents are complementary. The optical purities of the alcohols obtained from the hydroboration of disubstituted T-alkenes or trisubstituted alkenes with monoisopinocampheylborane are high (Table 2) and increase with an increase in the steric... 

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. 

Application of Various Chiral Reagents Derived from IpciBH. Diisopinocampheylborane does not normally yield satisfactory ee s in hydroboration reactions of 1,1-disubstituted alkenes, /rans-alkenes, or trisubstituted alkenes. This problem has been partially solved by the introduction of Monoisopinocam-pheylborane, IpcBHa, which is derived from IPC2BH. IpcBH2 handles frans -alkenes and trisubstituted alkenes effectively, since... 

Asymmetric Hydroboration. The steric requirements of IpcBH2 are such that hydroboration of trans and trisubstituted alkenes proceeds with little or no displacement of a-pinene from the reagent, a phenomenon which is observed with the more hindered Diisopinocampheylborane (IpC2BH). Ipc2BH is most effective for the hydroboration of relatively unhindered cis alkenes,... 

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. 

Asymmetric hydroborations of several heterocyclic alkenes with diisopinocampheylborane appear to be particularly favorable, resulting in products of almost 100% enantiomeric purity (e.g. equation 53). The reagent has also been used in asymmetric syntheses of a number of complex molecules. Discussion is beyond the present scope but a single example is given as an illustration (equation 54). °... 

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