Asymmetric hydroboration of alkenes

A simple example of the use of these chiral reagents is provided by the chiral hydroboration of Z-but-2-ene. Note that cleavage with iodine results in inversion at the stereogenic centre, unlike the other methods, which give retention. 

The chiral hydroboration works particularly well with cyclic alkenes. It is a key step in an elegant asymmetric synthesis of loganin (81) and can be seen in action again in section 7.3.1. 

As noted above, only cyclic andZ-alkenes work well with IpC2BH. To obtain good optical yields with E- or trisubstituted alkenes, it is necessary to use IpcBH2 as in the example below. 

4 Asymmetric reduction using chiral boranes andborohydrides  

Alpine borane is the delightful trivial name of the trialkylborane obtained from 9-borabicyclo[3.3.1]nonane and (+)- or (-)-a-pinene. 

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There are two common ways to accomplish an asymmetric reaction. Either a second chiral center is created in a molecule under the influence of an existing chiral center in that molecule or a chiral reagent acts on a prochiral substrate to create a new chiral center. The conversion of chiral a-keto esters to di-, astereomeric a-hydroxy esters is an example of the first type of asymmetric reaction, and the asymmetric hydroboration of alkenes with chiral boranes is an example of the second type (Fig. 1). 

Asymmetric reaction is one of the most exciting features of catalyzed hydroboration since optically active phosphine ligands are the chiral auxiliaries most extensively studied for metal-catalyzed reactions (Scheme 13).134 The chiral ligands used for asymmetric hydroboration of alkenes include BINAP,136 1 03-106,167-170 QUINAP,171-173 107-109,172,174-176 and BDPP.177,178... 

Table 2 Asymmetric hydroboration of alkenes with HBcat 80...

DBNE is highly enantioselective for the alkylation of aliphatic aldehydes (Table 2, entries 5-11) as well as for the alkylation of aromatic aldehydes (Table 2, entries 1—4). Most of the other types of chiral catalysts are effective only for the alkylation of aromatic aldehydes. Thus, various types of optically active aliphatic alcohols are first synthesized using DBNE (Table 2, entries 5-11). (It should be noted that the structures of aliphatic alcohols synthesized by asymmetric reduction of ketones or by asymmetric hydroboration of alkenes have been somewhat limited.)... 

The first enantioselective asymmetric synthesis with ee in the range of 90% was the asymmetric hydroboration of alkenes desoibed in 1961 by H. C. Brown et al. In this cl sic study (Rgure 3), (R)-(-)2 butanol of 90% ee was isolated using ccmunercial (+)-a-pinene of about 90% ee. More recently, the authors prepared enantiopure a-pin ie and wo e able to produce 2-butanol with 98% ee. Asynunetric hydroboration became an established and an important class of asymmetric syntheses with very high ee s. 

Figure 4, Model for the relevant steric features of3 which lead to enantiofacial selectivity in the asymmetric hydroboration of alkenes. The preferred orientations are shown for several representative alkene substrates.

Sato, M. Miyaura, N. Suzuki, A. Rhodium(i)-catalyzed Asymmetric Hydroboration of Alkenes with 1,3,2-benzodioxaborole. Tetrahedron Lett. 1990,31,231-234. 

We note that there are NMR-based kinetic studies on zirconocene-catalyzed pro-pene polymerization [32], Rh-catalyzed asymmetric hydrogenation of olefins [33], titanocene-catalyzed hydroboration of alkenes and alkynes [34], Pd-catalyzed olefin polymerizations [35], ethylene and CO copolymerization [36] and phosphine dissociation from a Ru-carbene metathesis catalyst [37], just to mention a few. 

Asymmetric hydroboration.1 The key step in a synthesis of natural (+ )-hir-sutic add-C (1), based on an earlier synthesis of racemic 1, is an efficient asymmetric hydroboration of the meso-alkene 2. Reaction of 2 with (+ )-diisopinocampheyl-borane (90% ee) followed by oxidation provides the exo-alcohol 3 in 73% yield and in 92% optical purity. Ring expansion of the corresponding ketone with ethyl diazoacetate is not regioselective even in the presence of BF3 etherate or (C2H5)30+ BF4, but does afford the desired a-keto ester in the presence of SbCl5 (8, 500-501). Decarboxylation of the crude product gives (— )-4 in 90% ee after chromatography. 

Asymmetric hydroboration.2 In a review of asymmetric hydroboration, Brown el al. conclude that this is the preferred reagent for asymmetric hydroboration of unhindered n j-alkenes. Thus, (R)-(—)-2-butanol can be prepared from cis-2-butene with ( —)-l in 98% ee and (S)-( + )-2-butanol is obtained using (+)-l in 95% ee. The alcohols obtained in this way have the same absolute configuration. 

This reaction is useful for asymmetric hydroboration of m-disubstituted alkenes to give highly pure optically active alcohols, but is less useful in the case of 1,1-disubstituted, frans-disubstituted, or trisubstituted alkenes. 

Chiral ketones.3 Asymmetric hydroboration of a prochiral alkene with monoisocampheylborane followed by a second hydroboration of a nonprochiral alkene provides a chiral mixed trialkylborane. This product reacts with acetaldehyde with elimination of a-pinene to give a chiral borinic acid ester in 73-100% ee. Treatment of this intermediate with a,a-dichloromethyl methyl ether (2,120 5, 200-203) and lithium triethylcarboxide followed by oxidation results in an optically active ketone in 60-90% ee. 

Asymmetric hydroboration of prochiral alkenes has been achieved using transition metal catalysts and chiral phosphines as ligands to obtain enantiomerically pure alkyl boronates <1997CC173>. Catalysts such as Rh(COD)2+BF4 , Rh(COD)2+Cl, Rh+BF4 , etc., in combination with chiral phosphines like DIOP 71, BINAP 72, CHIRAPHOS 73, DIPAMP 74, BDPP 75, ferrocene-based diphosphines 76<1999TL4977>, etc., have been employed for the asymmetric hydroboration of prochiral alkenes with moderate to high ee (DIOP = 2,3-0-isopropylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)butane BINAP = 2,2-bis(diphenyl-phos-phanyl)-l,1-binaphthyl CHIRAPHOS = 2,3-bis(diphenylphosphino)butane DIPAMP = l,2-bis[(2-methoxyphe-nyl)phenylphosphino]ethane BDPP = 2,4-bis(diphenylphosphino)pentane). 

Asymmetric hydroboration.1 Hydroboration of alkenes with catecholborane catalyzed by Rh(COD)Cl-2BINAP or [Rh(COD)Cl]2-2DIOP and followed by oxidation provides optically active alcohols in 20-75% ee Rh-BINAP systems are somewhat more enantioselective than Rh-DIOP systems. 

Asymmetric hydroboration of prochiral alkenes with monoisopinocampheyl-borane in the molar ratio of 1 1, followed by a second hydroboration of non-prochiral alkenes with the intermediate dialkylboranes, provides the chiral mixed trialkylbo-ranes. Treatment of these trialkylboranes with acetaldehyde results in the selective, facile elimination of the 3-pinanyl group, providing the corresponding chiral borinic acid esters with high enantiomeric purities. The reaction of these intermediates with base and dichloromethyl methyl ether provides the chiral ketones (Eq. 130) . A simple synthesis of secondary homoallylic alcohols with excellent enantiomeric purities via B-allyldiisopinocampheylborane has been also reported... 

Reviews on the synthesis of chiral alcohols by asymmetric hydroboration of prostereogenic alkenes have been published47-53 and this topic is also covered in Houben-Weyl, Vol. 6/la, pp 494-553. The synthesis of asymmetric hydroborating agents, and their reactivity and enan-tioselectivity in reactions with major classes of prostereogenic alkenes, is also described in Sections D.2.5.2.1.2. and D.2.5.2.1.3. 

Asymmetric Hydroboration. Rhodium complexes are known to catalyze hydroboration of alkenes with unreactive borane derivatives, e.g. catecholborane and oxaborolidine. This reaction proceeds enantioselectively by use of BINAP as a ligand for neutral " or cationic rhodium complexes. Reaction of styrene with catecholborane followed by oxidation affords (R)-1-phenylethanol in 96% ee in the presence of (R)-BINAP and [Rh(cod)2]Bp4 (eq 5). ... 

Later, Brown and co-workers developed the method described above for the preparation of enantiomerically pure Ipc2BH (>99% ee) and applied the reagent in the asymmetric hydroboration of prochiral alkenes. Oxidation of the trialkylboranes provided optically active alcohols. In the case of cis-alkenes, secondary alcohols were obtained in excellent enantiomeric purity (Figure 1). The reaction is general for most types of cw-alkene, e.g. C(S-2-butene forms (R)-2-butanol in 98.4% ee, and c(s-3-hexene is converted to (R)-3-hexanol in 93% ee. However, the reagent is somewhat limited in reactions with unsymmetrical alkenes e.g. c/s-4-methyl-2-pentene yields 4-methyl-2-pentanol with 96% regioselectivity but only 76% ee (Figure 1). ... 

Asymmetric hydroborations of heterocyclic alkenes are highly regio- and enantioselective. For example, hydroboration of 2,3-dihydrofuran with Ipc2BH followed by oxidation provides 3-hydroxyfuran in 83% ee, which can be upgraded to essentially the enantiomerically pure form (>99% ee) (Figure 2). ... 

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