Diisopinocampheylborane asymmetric hydroboration

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. 

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. 

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. 

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. 

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,... 

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). °... 

Brown, H. C., Bhat, K. S., Jadhav, P. K. Chiral synthesis via organoboranes. Part 32. Synthesis of B-(cycloalk-2-enyl)diisopinocampheylboranes of high enantiomeric purity via the asymmetric hydroboration of cycloalka-1,3-dienes. Successful asymmetric allylborations of aldehydes with B-(cycloalk-2-enyl)diisopinocampheylboranes. J. Chem. Soc., Perkin Trans. 1 1991, 2633-2638. 

Among dialkylboranes, diisopinocampheylborane (lpc2BH, 1) is most often used for asymmetric hydroboration and several procedures for its synthesis are known2 67-71. The most convenient one, providing a product of essentially 100% ee, involves the hydroboration of ot-pinene with boranc-dimethyl sulfide complex71. 

Monoisopinocampheylborane (IpcBH2), a relatively unhindered hydroborating agent, reacts readily with all classes of alkenes93,104. Enantioselectivity of the addition to unhindered (Z)-alkenes is low, whereas more hindered ( )-isomers and trisubstituted alkenes react with much higher selectivity. Thus, mono- and diisopinocampheylborane are complementary asymmetric hydroborating agents69,93. 

In summary, only frorw-2,5-dimethylborolane, which is not readily available, consistently gives products of high optical purity with three major classes of olefins. In addition, relatively unhindered (Z)-olefms arc the only class handled well by diisopinocampheylborane. Consequently, the range of organoboranes directly produced in high optical purity by asymmetric hydroboration is rather limited. Fortunately, mono- and diisopinocampheylborane derivatives have several features which allow their optical purity to be upgraded to essentially 100% ee. 

Table 5.6. Asymmetric Hydroboration of Heterocyclic Compounds with Diisopinocampheylborane.

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. 

Brown, H. C. Desai, M. C. Jadhav, P. K. 1982. Hydroboration. 61. Diisopinocampheylborane of high optical purity, improved preparation and asymmetric hydroboration of representative cis-disubstituted... 

The first asymmetric synthesis to achieve >90% optical yield was Brown s hydroboration of cis alkenes with diisopinocampheylborane (IpC2BH, Figure 7.10) in 1961 [130,131], The reagent was prepared by hydroboration of a-pinene of 90% ee 2-butanol obtained from hydroboration/oxidation of cw-2-butene had an optical purity of 87%, indicating an optical yield of 90%. ci5-3-Hexene was hydroborated in -100% optical yield. Since then, simple methods for the enantiomer enrichment of lpc2BH (and IpcBH2) have been developed [132-134], and enantioselectivities have been evaluated more carefully with the purified material. For example, lpc2BH of 99% ee affords 2-butanol (from cw-2-butene) in 98% ee and 3-hexanol (from ci5-3-hexene) in 93% ee, both determined by rotation (see Table 7.6, entries 1 and 5) [132]. ... 

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... 

The reaction of organoboranes with carbon-nitrogen multiple bonds always leads to aminoborane derivatives through a hard-hard interaction. Hydro-boration of nitriles with optically active diisopinocampheylborane (43) constitutes a key step in an asymmetric synthesis of amino acids (44). Carbonyl compounds are deoxygenated via hydroboration of their tosylhydrazones (45). 

---