Alkenes asymmetric hydroborations

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. 

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.

Fig. 2.10 Applications of asymmetric hydroboration with diphosphine catalysts to meso-symmetric alkenes. For 10(a), iridium complexes reverse the sense of enantioselectivity in up to 54% enantiomeric excess.

Asymmetric hydroboration.1 Hydroboration of phenyl-substituted trisubstituted alkenes, cyclic or acyclic, followed by oxidation results in alcohols with an optical purity of 80 100%, with the (S)-configuration at the hydroxylaled carbon predominating with reagent prepared from (+)-oc-pinene. 

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 With the exception of 1,1-disubstituted ethyl-enes, a wide variety of alkenes including 1,1,2-trisubstituted alkenes undergo hydroboration with (R,R)- or (S,S)-1 in 70-90% yield and with high enantioselectivity (97-100% ee). 

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. 

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. 

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). 

The efficiency of asymmetric hydroboration is high if one approach trajectory leads to severe steric interactions between the hydroborating reagent and the alkene and the approach trajectory to the other face of the alkene involves relatively insignificant steric interactions, i.e. the energy difference between the two transition states is large. It should be noted, however, that if both approaches involve major steric interactions then a decrease in overall reactivity will be observed. 

Asymmetric hydroboration followed by oxidation is used to give optically active alcohols. For example, addition of (+)-IpcBH2 to 1-phenylcyclopentene followed by oxidation gives S,2R)-trans-2-phenylcyclopentanol in 100% e.e. (Equation B2.9). The structure of the product alcohol reveals that the homochiral hydroborating reagent encounters fewer unfavourable steric interactions with alkene substituents if it approaches the lower face of the alkene as drawn in Equation B2.9. This preference determines the absolute stereochemistry of the product. (The regiochemistry and relative stereochemistry of the product are determined by fundamental hydroboration characteristics.)... 

Fig. 3.30. Asymmetric hydration of an achiral alkene via hydroboration/oxidation/hydro lysis AFa corresponds to the extent of reagent control of diastereoselectivity.

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 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 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...

The kinetic resolution of racemic alkenes 112 was demonstrated in asymmetric hydroboration with Rh-QUINAP catalyst. A 78% yield with 98% ee was achieved when using 0.6 equiv. of HBcat compared to the alkene.180... 

Asymmetric hydroboration 2171 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)2l8>. A simple synthesis of secondary homoallylic alcohols with excellent enantiomeric purities via B-allyldiisopinocampheylborane has been also reported 219),... 

Asymmetric hydroboration.1 Hydroboration of 1-phenyl-1-cyclopentene with IpcBH2 (100% ee) results in a dialkylborane (1) containing the traws-2-phenylcyclopentyl group of 100% ee. However, hydroboration of prochiral trisubstituted alkenes usually results in alkylisopinocampheylboranes of 50-85% ee. Most of these products are solids, and selective crystallization (usually from ether) can give the optically pure dialkyboranes. In some cases resolution can be achieved by allowing the impure borane to age for several... 

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. 

Table 3. Selected Chiral Alcohols via Catalytic Asymmetric Hydroboration/Oxidation of Alkenes with 1,3,2-Benzodioxaborole...

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). ... 

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