Alkene Hydroboration, diastereoselective

Acyclic diastereoselective hydroboration,J Hydroboration-oxidation of terminal alkenes substituted at C4 by a large and a medium alkyl group can proceed asymmetrically with BH3 S(CH,)2 or, even more selectively, with thexylborane. Example ... 

Remarkable regioselectivity was observed in the thermal migration of the tetra-substituted alkene Z-83. Hydroboration of this compound furnishes only the migration product in the direction of the ethyl group. Furthermore, the migration was stereoselective providing, after the standard amination sequence, the benzylic amine 85 in 46% yield. The diastereoselectivity was 95 5 between C(l) and C(2) and >99 1 between C(2) and C(3) (Scheme 17) [7, 8, 13],... 

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. 

The conclusion drawn from Section 3.4.1 for the hydroborations to be discussed here is this an addition reaction of an enantiomerically pure chiral reagent to a C=X double bond with enantiotopic faces can take place via two transition states that are diastereotopic and thus generally different from one another in energy. In agreement with this statement, there are diastereoselective additions of enantiomerically pure mono- or dialkylboranes to C=C double bonds that possess enantiotopic faces. Consequently, when one subsequently oxidizes all C— B bonds to C—OH bonds, one has realized an enantioselective hydration of the respective alkene. 

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

We thus summarize the yield ratios of the conceivable hydroboration products E, F, G, and H should be much little little none. One enantiomer of E comes from the reaction of the S-alkene with the, S, S -borane the other enantiomer of E comes from the reaction of the //-alkene with the //.//-borane. Thus, each enantiomer of the reagent has preferentially reacted with one enantiomer of the substrate. The diastereoselectivity of this reaction thus corresponds to a mutual kinetic resolution. 

These bulkier boranes enhance the regio selectivity of hydrobora tion of trisubstituted alkenes in particular and may also lead to high diastereoselectivity when there is a stereogenic centre next to the alkene. In this next examplej an allylic alcohol is hydroborated with thexyl borane. Oxidation reveals complete regioselectivity and a 9 1 stereoselectivity in favour of hydroboration on the same side as the OH group. 

With acyclic asymmetric compounds high levels of diastereoselection are achieved in the hydroboration/oxidation of those alkenes with preexisting allylic stereogenic centers. 

The hydrosilylation-oxidation of simple unfunctionalized alkenes has not been widely used for the diastereoselective preparation of alcohols, probably because it would not in general be expected to give very different results to hydroboration oxidation. One example which has been reported is the exo-selective hydrosilylation of norbornene (1) with trichlorosilane and hexachloroplatinic acid6, followed by oxidation to c.vo-norbornanol (2)1. 

To achieve diastereoselectivity in electrophilic additions to a double bond in acyclic compounds, there must be a facial preference for attack. An A strain provides such an element for conformational control, as exemplified by hydroboration of the alkene shown below.The hydration of a double bond via hydroboration involves (1) anti-Markovnikov addition of the B-H bond, (2) cis addition of the B-H bond, (3) addition of the B-H bond from the less hindered side of the double bond, and (4) oxidation with retention of configuration. 

The hydroboration of non-aromatic alkenes is regio- and diastereoselective. Only the reaction of styrene derivatives such as 24 results in mixtures of regio-isomers (25 and 26) Eq. (12). 

Bauer and Maier synthesized the benzolactone 538, which has the core structure of salicylihalamide A, using intramolecular Suzuki reaction.228 Hydrobora-tion of the alkenyl iodide-alkene 537 with 9-BBN and subsequent Suzuki reaction in the presence of a palladium catalyst gave the macrolactone 538 in 48% yield (Scheme 160). The hydroboration proceeded with high diastereoselectivity. 

Lonomycin A is a structurally complex polyether antibiotic whose array of sensitive functionalities poses a considerable synthetic challenge. A rhodium-catalyzed hydroboration of a 1,1-disubstituted alkene has been applied by Evans and Sheppard to the penultimate step in the construction of a lonomycin Ci-Cn synthon. " High diastereoselectivities were observed for the desired Cn... 

The hydroboration of olefins is a classic reaction in organic synthesis. - Dialkylbo-ranes add rapidly to alkenes in the absence of catalyst. However, dialkoxyboranes, such as catecholborane and pinacolborane, add more slowly to olefins and alkynes. Thus, transition metal complexes could catalyze the addition of dialkoxyboranes to olefins and alkynes without interference from the background reaction. The potential to alter chemoselectivity, regioselectivity, enantioselectivity, and diastereoselectivity has led a munber of groups to develop metal-catalyzed versions of hydroboration. " Enantioselective hydroboration would alleviate the need to use boranes containing stoichiometric amounts of chiral substituents to generate optically active alkylboranes. 

Recently total syntheses of the enolized P-diketones trikentriorhodin (39) and the 9-cis isomer of mytiloxanthin (38) with known stereochemistry at all chiral centres have been reported in brief (57). The route utilized the same intermediate methyl ketone used earlier in the total synthesis of capsorubin (66), although it was prepared from (-t- )-camphor by a different approach involving diastereoselective introduction of the chiral centre by hydroboration of an alkene intermediate. Synthetic (38) had chromatographic, IR, NMR and MS properties consistent with published data (5) the CD maxima appear to correspond to those of natural trikentriorhodin subsequently reported (59). However, the Cotton effect is very weak (59, 57). Comparative CD data for synthetic 9-cis (38) and the 9-cis isomer of natural mytiloxanthin were not given. 

This method has been applied to the synthesis of polyhydroxylated indolizidines [62]. For example, alkenylboronate ester 70, prepared by hydroboration of 1-acetoxy-but-3-yne, underwent highly diastereoselective addition to the diol 68 in the presence of BFj OEtj (Scheme 7.15). Elaboration of the alkene functionality of 71 by dihy-droxylation, followed by a cyclization approach using reductive amination led to the target molecule 6-deoxycastanospermine (72). 

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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