Asymmetric hydroborations

7i-withdrawing ones. In all cases the U-alkene was obtained as the major product, but the selectivities remained modest (Equation (13.8)). 

NHC ligands have led to great advances in metal catalysis thanks to their high stability and reactivity of the resulting species. However, the reaction conditions for reduction processes need to be carefully optimized to avoid irreversible cleavage of NHC from metal. For these transformations, sterically hindered and donor functional NHC ligands have played an important role. 

But asymmetric applications remain arguably the area to further develop since with notable exceptions, the level of chiral induction for these reactions remains disappointing. Hopefully the known studies will lead to new strategies for the development of more reactive and selective catalysts in the reduction of multiple bonds. 

Marciniec, (ed.). Comprehensive Handbook on Hydrosilylation, Elsevier, Oxford, 1992. 

Poyatos, A. Maisse-Frangois, S. Bellemin-Laponnaz and L. H. Gade, Organometallics, 2006, 25, 2634-2641. 

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One of the newer and more fmitful developments in this area is asymmetric hydroboration giving chiral organoboranes, which can be transformed into chiral carbon compounds of high optical purity. Other new directions focus on catalytic hydroboration, asymmetric aHylboration, cross-coupling reactions, and appHcations in biomedical research. This article gives an account of the most important aspects of the hydroboration reaction and transformations of its products. For more detail, monographs and reviews are available (1—13). 

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... 

There have been several reviews of asymmetric synthesis via chiral organoboranes (6,8,378,382,467—472). Asymmetric induction in the hydroboration reaction may result from the chiraHty present in the olefin (asymmetric substrate), in the reagent (asymmetric hydroboration), or in the catalyst (catalytic asymmetric hydroboration). 

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. 

EinaHy, kinetic resolution of racemic olefins and aHenes can be achieved by hydroboration. The reaction of an olefin or aHene racemate with a deficient amount of an asymmetric hydroborating agent results in the preferential conversion of the more reactive enantiomer into the organoborane. The remaining unreacted substrate is enriched in the less reactive enantiomer. Optical purities in the range of 1—65% have been reported (471). 

Catalytic Asymmetric Hydroboration. The hydroboration of olefins with catecholborane (an achiral hydroborating agent) is cataly2ed by cationic rhodium complexes with enantiomericaHy pure phosphines, eg, [Rh(cod)2]BE4BINAP, where cod is 1,5-cyclooctadiene and BINAP is... 

Dilongifolyl borane [77882-24-7] M 422.6, m 169-172 . Wash with dry Et20 and dry in a vacuum under N2. It has m 160-161 in a sealed evacuated capillary. It is sparingly soluble in pentane, tetrahydrofuran, carbon tetrachloride, dichloromethane, and chloroform but the suspended material is capable of causing asymmetric hydroboration. Disappearance of solid indicates that the reaction has proceeded. [J Org Chem 46 2988 1981.]... 

The hydroboration of enynes yields either of 1,4-addition and 1,2-addition products, the ratio of which dramatically changes with the phosphine ligand as well as the molar ratio of the ligand to the palladium (Scheme 1-8) [46-51]. ( )-l,3-Dienyl-boronate (24) is selectively obtained in the presence of a chelating bisphosphine such as dppf and dppe. On the other hand, a combination of Pdjldba), with Ph2PC6p5 (1-2 equiv. per palladium) yields allenylboronate (23) as the major product. Thus, a double coordination of two C-C unsaturated bonds of enyne to a coordinate unsaturated catalyst affords 1,4-addition product On the other hand, a monocoordination of an acetylenic triple bond to a rhodium(I)/bisphosphine complex leads to 24. Thus, asymmetric hydroboration of l-buten-3-yne giving (R)-allenyl-boronate with 61% ee is carried out by using a chiral monophosphine (S)-(-)-MeO-MOP (MeO-MOP=2-diphenylphosphino-2 -methoxy-l,l -binaphthyl) [52]. 

I 7 Hydroboration, Diboration, Silylboration and Stonnylbomtion Tab. 1-6 Asymmetric Hydroboration... 

This route can be used to prepare enantiomerically enriched organozinc reagents by asymmetric hydroboration (see Section 4.5.3), followed by exchange with diisopropyl-zinc. Trisubstituted cycloalkenes such as 2-methyl or 2-phenylcyclohexene give an enantiomeric purity greater than 95%. The exchange reaction takes place with retention of configuration.137... 

Formal hydration of the double bond appeared by the hydroboration-oxidation sequence. Desymmetrization reactions with catalytic asymmetric hydroboration are not restricted to norbornene or nonfunctionalized substrates and can be successfully applied to meso bicyclic hydrazines. In the case of 157, hydroxy derivative 158 is formed with only moderate enantioselectivity both using Rh or Ir precatalysts. Interestingly, a reversal of enantioselectivity is observed for the catalytic desymmetrization reaction by exchanging these two transition metals. Rh-catalyzed hydroboration involves a metal-H insertion, and a boryl migration is involved when using an Ir precatalyst (Equation 17) <2002JA12098, 2002JOC3522>. 

Early work in the field of asymmetric hydroboration employed norbornene as a simple unsaturated substrate. A range of chiral-chelating phosphine ligands were probed (DIOP (5), 2,2 -bis(diphenyl-phosphino)-l,l -binaphthyl (BINAP) (6), 2,3-bis(diphenylphosphino)butane (CHIRAPHOS) (7), 2,4-bis(diphenylphosphino)pentane (BDPP) (8), and l,2-(bis(o-methoxyphenyl)(phenyl)phos-phino)ethane) (DIPAMP) (9)) in combination with [Rh(COD)Cl]2 and catecholborane at room temperature (Scheme 8).45 General observations were that enantioselectivities increased as the temperature was lowered below ambient, but that variations of solvent (THF, benzene, or toluene) had little impact. 

Table 4 Enantioselectivities for [Rh(COD)2]+/L catalyzed asymmetric hydroboration of styrene.

However, by far the most common approach toward catalytic asymmetric hydroboration is to use a chiral catalyst and an achiral borane source. Both homobidentate F Pand heterobidentate P,N ligand classes have been employed in this transformation with varying degrees of success. 

Figure 2 Chiral diphosphine ligands for asymmetric hydroboration.

The third major class of diphosphine ligands employed in catalytic asymmetric hydroboration are those possessing planar chirality (Figure 6). These ligands are chiral by virtue of the non-symmetrical disubstitution of one of the cyclopentadienyl rings. 

Figure 14 Common drugs potentially prepared by asymmetric hydroboration.

An asymmetric version of the Pd-catalyzed hydroboration of the enynes was reported in 1993(118]. The monodentate phosphine (S)-MeO-MOP was used as a chiral ligand for the palladium catalyst. Enantioselectivity of the asymmetric hydroboration was estimated from the enantiopurity of homopropargyl alcohols, which were obtained from the axially chiral allenylboranes and benzaldehyde via an SE pathway (Scheme 3.78). 

Fig. 2.9 Template structures for the intermediate in catalytic asymmetric hydroboration with alkene, ligand, catechoborane and hydride coordinated, (a) R-BINAP and (b) R-QUINAP. E-propenylbenzene is illustrated to show the increased steric hindrance to the alkene in the BINAP case.

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