Hydroboration facial selectivity

Klein showed that axial reaction of the parent methylenecyclohexane 37 is preferred in hydroboration [106], The experimental data on the parent methylenecyclohexanone 37a accumulated by Senda et al. [107] and the more recent systematic studies by Cieplak et al. [108, 109] on jr-facial selectivities of 3-substituted methylene-cyclohexanes 37 have characterized the intrinsic features of the facial selection of methylenecyclohexanes. That is, axial preference of unsubstituted and 3-substituted methylenecyclohexanes was observed in oxymercuration [107] and epoxidation reactions [110], There is also an increase in the proportion of axial attack with increase in the electronegativity of the remote 3-equatorial... 

Scheme 4.9 gives some examples of the use of boranes in syntheses of alcohols, aldehydes, ketones, amines, and halides. Entry 1 demonstrates both the regioselec-tivity and stereospecificity of hydroboration, resulting in the formation of trans-2-methylcyclohexanol. Entry 2 illustrates the facial selectivity, with the borane adding anti to the endo methyl group. 

A wide range of catalysts is now known that will bring about B H addition to simple terminal alkenes. For group 9 complexes, catalytic activity follows the order [(dppe)Rh (nbd)]+ > [Rh(PPh3)3Cl] > [(COD)Ir(PCy3)(C5H5N)]+ (where dppe = 2-bis(diphenylphosphino) ethane and nbd = norbornadiene).19 Different facial selectivity is found for catalytic hydroboration reactions of these compounds with chiral alkenes (Equation (1)). Thus, [(dppe)Rh(nbd)]+ gives... 

Facial selectivity in electrophilic additions (carbene addition, mercuration, epoxi-dation, and hydroboration) to 4-substituted 9-methylenenorsnoutanes (1) as model alkenes has been elucidated and the observed preference for yyn-attack (Table 1)... 

The investigation of factors affecting facial selectivity in the hydroboration of steroidal -alkenes revealed the facial (a vs /3) stereoselectivities of hydroboration of androst-5-enes (69) and B-norandrost-5-enes (70) do not parallel the difference between the calculated force-field energies for a- and jS-cyclobutane models (71)-(74). This finding appears to suggest that the facial selectivity is not determined by the four-centre transition state but by the relative ease of formation of the initial tt-complex. ... 

The first facially selective hydroboration of a 5-methyhdene[2.2.1]bicychc intermediate has also recently been reported. The rhodium-catalyzed hydroboration of the methylidene group with HBcat proved superior to stoichiometric borane or dialkylborane reagents, in terms of higher diastereomeric excess and chemical yields (equation 15). For instance, while borane gave 89% of the desired 5-endo product along with 11% of the 5-exo product, the catalyzed variant with HBcat gave 95% for the desired 5-endo product when the reaction was run at room temperature. No improvement in diastereoselec-tivity was observed when reactions were run at lower temperatures. 

Sodium acetoxytrihydroborate is also effective,while certain titanium, rhodium and cobalt complexes catalyze hydroborations with sodium tetrahydroborate." In the latter case the facial selectivities can be quite different from, even opposite to, those observed with borane-THF. ... 

If a prochiral ketone or alkene does not have any significant inbuilt structural characteristics that induce a reagent to attack one face or the other, it is still possible to achieve a high degree of facial selectivity, and so one can obtain a product of high enantiomeric purity. An example is provided by the asymmetric hydroboration of prochiral alkenes. 

Laboratory attempts to make, say, an enantiomerically pure compound are frequently based on creation of reagents that exhibit high facial selectivity. One cited example was asymmetric hydroboration, which gives alcohols of high enantiomeric purity. 

Abstract The A(1,2) and A(1,3) strains and their control on the conformational and reactivity profiles of substrates are discussed. The application of A(1,3) strain to the facial selectivity of reactions such as [2,3] and [3,3] sigmatropic shifts, intramolecular SN2 reactions, hydroboration, enolate alkylation, etc. is highlighted. The high diastereoselectivity observed in the reactions of enolates derived from 4-substituted /V-al kanoyl-1,3-oxazolidinones (Evans enolates) with electrophiles is discussed. 

The facial selectivity of (43) was found to be 1.75 1 from the ratio of aldol products (48) and (49) obtained by the reaction with the achiral boron enolate (50). The latter is structurally similar to reagents (37) and (38). These experiments confirm again the validity of the rule of double asymmetric synthesis. The product (44) can be further converted through a sequence of reactions to provide (+)-Prelog-Djerassi lactonic acid (51 Scheme 27) (i) trimethylsilylation (ii) hydroboration with thexylborane (single asym-... 

The investigation of factors affecting facial selectivity in the hydroboration of steroidal -alkenes revealed the facial (a vs /3) stereoselectivities of hydroboration of androst-... 

The e o-facial selectivity, observed in the hydroboration of 2-, 3-, and 4-methylene-5o -androstanes (96)-(98) (Scheme 10), has been rationalized in terms of the easier steric access and a hyperconjugative interaction of the alkene with the adjacent axial C-H bonds enhancing the electron density on one face of the alkene (99). ... 

Asymmetric induction increases with increasing steric demands of the alkene, and cis alkenes show the worst selectivity. This can be explained by three-dimensional drawing 149, which shows approach of re,si face of ct[r-2-butene with the less sterically hindered case of the methyl groups down (when the methyl groups are up there is a severe interaction). If cis-2-butene is rotated by 180° along the axis which bisects the C=C bond (C=/=C), the other face (the si,re face) of the alkene is exposed to reaction. There is no facial bias for approach of the cis alkene and, therefore, little or no enantioselectivity in the hydroboration reaction. Examination of 150 for approach of trans-2-hutene from the left face of the pinanyl horane reagent shows... 

Diastereoselective osmylation and hydroboration of, y-unsaturated (V,(V-diisoprop-ylamides (100)-(1 2) have been reported to occur with useful diastereofacial selectivity (Scheme 11). The major diol isomer from (E)-alkenes (100) and (101), in the presence of TMEDA at -78 °C, corresponds to the facial preference shown in transition-state model (103) [(100) gave an 11 1 preference at -78 °C (101) afforded the same ratio at —78 °C, and 6 1 at room temperature], while the opposite preference for (104) is observed with the (Z)-alkene (102) (>20 1 at —78°C and 7 1 at room temperature). Hydroboration with 9-BBN does not show this inversion of diastereofacial selectivity for the (Z)-alkene all of the results correspond to the usual preference for a transition state such as (105). ... 

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