Substrate-controlled hydroboration

This perfectly substrate-controlled hydroboration opens the path to a number of stereoselective aUyl functionalizations. While regioselectivity can be quite satisfactorily controlled in the hydroboration, it created, at least at the beginning, a few problems with the hydroformylation reaction. 

Hupe, E. Calaza, M. I. Knochel, P. Substrate-controlled highly diastereoselective synthesis of primary and secondary diorganozinc reagents by a hydroboration/B-Zn exchange sequence. Chem. Eur. J. 2003, 9, 2789-2796. 

The stereochemical result is no longer characterized solely by the fact that the newly formed stereocenters have a uniform configuration relative to each other. This was the only type of stereocontrol possible in the reference reaction 9-BBN + 1-methylcyclohexene (Figure 3.25). In the hydroborations of the cited chiral alkenes with 9-BBN, an additional question arises. What is the relationship between the new stereocenters and the stereocenter(s) already present in the alkene When a uniform relationship between the old and the new stereocenters arises, a type of diastereoselectivity not mentioned previously is present. It is called induced or relative diastereoselectivity. It is based on the fact that the substituents on the stereocenter(s) of the chiral alkene hinder one face of the chiral alkene more than the other. This is an example of what is called substrate control of stereoselectivity. Accordingly, in the hydroborations/oxidations of Figures 3.26 and 3.27, 9-BBN does not add to the top and the bottom sides of the alkenes with the same reaction rate. The transition states of the two modes of addition are not equivalent with respect to energy. The reason for this inequality is that the associated transition states are diastereotopic. They thus have different energies—just diastereomers. 

In the discussion of the hydroboration in Figure 3.26, you saw that one principle of stereoselective synthesis is the use of substrate control of stereoselectivity. But there are quite a few problems in stereoselective synthesis that cannot be solved in this way. Let us illustrate these problems by means of two hydroborations from Section 3.3.3 ... 

At the beginning of Section 3.4, we wondered whether 3-ethyl-l-methylcyclohexene could also be hydroborated/oxidized/hydrolyzed to furnish the cis, trans-con 11 gured alcohol. There is a solution (Figure 3.32) if two requirements are fulfilled. First, we must rely on the assumption made in Section 3.4.3 that this atkene reacts with the cyclic borane in such a way that the reagent control of stereoselectivity exceeds the substrate control of the stereoselectivity. Second, both the alkene and the borane must be used in enantiomerically pure form. 

Substrate-controlled diastereoselective hydroboration of protected chiral allylic alcohols [25-27] or amines [28, 29] with 9-BBN gives almost always anti selective products. On the other hand, catalyzed hydroboration in most of the cases using catecholborane as hydroborating agent tends to be syn selective [28-30] (Eq. 5.9). 

Brown s discovery of the hydroboration reaction in the 1950s opened new avenues for the selective functionalization of olefins. The recognition that acyclic olefins can have well-defined conformational biases allowed the development of diastereoselective, substrate-controlled processes and the advent of the principles of acyclic stereocontrol. Given the central role the hydroboration of olefins has played, it is hardly surprising that the earliest examples in this field involve such transformations. For the organic chemist, diastereoselective and enantioselective hydrometalation reactions have rapidly become an indispensable tool equally useful in simple olefin functionalizations and in the stereoselective construction of highly complex molecules. 

The retrosynthetic elimination of olefinic stereocenters (E or Z) was illustrated above by the conversion 147 => 148 under substrate spatial control. It is also possible to remove olefinic stereocenters under transform mechanism control. Examples of such processes are the retrosynthetie generation of acetylenes from olefins by transforms such as trans-hydroalumination (LiAlH4), ci5-hydroboration (R2BH), or ci -carbometallation... 

In an attempt to rationalize the factors that control selectivity in the Rh- and Ir-catalyzed hydroboration reactions, Fernandez and Bo [35] carried out experimental and theoretical studies on the H—B addition of catecholborane to vinylarenes with [M(C0D)(R-QUINAP)]BF4, (QUINAP = l-(2-diphenylphosphino-l-naphthyl) isoquinoHne). A considerable difference was found in the stability of the isomers when the substrate was coordinated to the iridium(I) or rhodium(I) complexes. In particular, the difference between pro-R B1 and pro-S B2 isomers was not so great when the metal center was iridium and not rhodium (Figure 7.1), which explains the low ee-values observed experimentally when asymmetric iridium-catalyzed hydroboration was performed. Structurally, the energy analysis of the n2 and Tti interactions [36] seems to be responsible for the extra stabilization of the B2 isomer in the iridium intermediates (Figure 7.1). The coordination and insertion of alkenes, then, could be considered key steps in the enantiodifferentiation pathway. 

The /3-lactone was formed by the cyclization of a 3-hydroxycarboxylic acid with sulfonyl chloride. An alternative synthesis attempted to control all stereochemical relationships in the molecule using the properties of silyl moieties attached to substrates and reagents <20040BC1051>. Stereoselective reactions of this type included the use of silyl groups in enolate alkylations, hydroboration of allylsilanes, and an anti Se2 reaction of an allenyl silane with an aldehyde and ry -silylcupration of an acetylene. The /3-lactone was again formed by the standard sulfonyl chloride cyclization method. 

Our earlier statements on substrate and reagent control of stereoselectivity during hydroborations are incorporated in Figure 3.25. Because of the obvious analogies between the old and the new reactions, the following can be predicted about the product distribution shown ... 

The first substrate which was asymmetrically hydroborated using IPC2BH was c/s -2-butene, and the enantiomeric purity of the product 2-butanol (87% ee) obtained in this preliminary experiment was spectacular (eq 2), since Ipc2BH was made from a-pinene of low optical purity. This reaction represents the first nonenzymatic asymmetric synthesis for achieving high enantioselectivity. Its discovery marked the beginning of a new era of practical asymmetric synthesis obtained via reagent control. ... 

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. 

In hydroboration reactions described in our previous study [17], two possible products were observed depending on the nature of the reactant dienes and the reaction conditions formation of cross-linked polymers, which precipitate out of solution, or formation of soluble, small-molecule products, which have been analyzed using B NMR. Previous analysis [17] of the experimental NMR data (reproduced here as Eigs. 5 and S6) suggested that a range of fully hydroborated product species were present. The substrates E6, 1,3-cycloheptadiene, 1,3-cyclooctadi-ene, G6, and E6 all yielded cross-Unked polymers, whereas substrates D8, B6, C6, and the control A4 all yielded clear solutions. Interestingly, the excess equivalents of borane used in the reaction can also affect the outcome of the reaction products for certain molecules, such as in the example of l,3,5,5-tetramethyl-l,3-cyclohexadiene (D6), which was seen to form a clear solution when only one equivalent of borane was used, but an insoluble precipitate was observed when two equivalents were used [17]. The clear solution of D6 eventually formed a precipitate after 2 h. 

Regioselectivity of the CuCl-catalysed hydroboration of propargylic alcohols and ethers R C=CCH(OR )R with Pin2B2 can be controlled (from 98 2 to 2 98) by the steric bulk of the OR group and the NHC ligand to copper. A rationale has been provided by assuming different approach of the reactive species to the individual substrates (87)-(89).S9... 

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