Haloalkynes hydroboration

As discussed in Sect. B.iii.b, (Z)-/3-substituted aUcenylboranes are obtainable via 1-haloalkynes hydroboration-1,2-hydride migration protocol.f f f Their Pd-catalyzed reactions with ( )- and (Z)-alkenyl electrophiles provide (Z,E)- and (Z,Z)-conjugated dienes, respectively (Scheme 53). 

Cis-olefins or cis./rjns-dienes can be obtained from alkynes in similar reaction sequences. The alkyne is first hydroborated and then treated with alkaline iodine. If the other substituents on boron are alkyl groups, a cis-olefin is formed (G. Zweifel, 1967). If they are cir-alkenyls, a cis, trans-diene results. The reactions are thought to be iodine-assisted migrations of the cis-alkenyl group followed by (rans-deiodoboronation (G. Zweifel, 1968). Trans, trans-dienes are made from haloalkynes and alkynes. These compounds are added one after the other to thexylborane. The alkenyl(l-haloalkenyl)thexylboranes are converted with sodium methoxide into trans, trans-dienes (E. Negishi, 1973). The thexyl group does not migrate. 

The coupling of alkenylboranes with alkenyl halides is particularly useful for the stereoselective synthesis of conjugated dienes of the four possible double bond isomers[499]. The E and Z forms of vinylboron compounds can be prepared by hydroboration of alkynes and haloalkynes, and their reaction with ( ) or (Z)-vinyl iodides or bromides proceeds without isomerization, and the conjugated dienes of four possible isomeric forms can be prepared in high purity. 

The pathway followed by the reaction is depicted in Figure B4.1. Methoxide anion adds to the a-haloalkenylborane generated by hydroboration of the haloalkyne, and induces migration of an alkyl group from the boron atom to the alkenyl carbon atom. The migration displaces halide anion from the alkenyl carbon atom and the centre is inverted. Finally protonolysis of the carbon-boron bond by acetic acid releases the (/f)-alkcne. 

An alternative procedure for the synthesis of (l-halo-l-alkenyl)boronates (X=Br, I) is hydroboration of haloalkynes with diisopinocanphylborane (eq (14)). 

The trialkylborane is derived from monoalkyl-(l,l,2-trimethylpropyl)borane by hydroboration. Care must be taken in the oxidation step leading to the a-chiral ketones and buffering is necessary to avoid racemization. However, even with these precautions, 2-6% racemization is observed in some cases9,20. The intermediate alkenyl-(l,l,2-trimethylpropyl)borinates are relatively resistant to oxidation thus prolonged reaction times or higher temperatures are sometimes required to complete the reaction via the haloalkyne route. 

Dihalo-l-alkenes From 1-haloalkynes, through hydroboration and treatment of the resulting 1-boryl-l-haloalkenes with CuBr2, a simple preparation is accomplished. 

BF3 Et20 to remove the methoxy moiety. The procedure has also been used for the preparation of cA-vinyl-9-BBN derivatives since the normal route to such derivatives based upon the hydroboration of 1-haloalkynes, followed by hydride-induced rearrangement gives ring expansion products competitively with (Z)-l-halovinyl-9-BBNs. " Similar behavior has been observed for the reaction of a-methoxyvinyllithium with B-alkyl-9-BBNs (see 1-Methoxyvinyllithium) ... 

Highly synthetically demanding (. -hisubstituted alkenes and their derivatives (useful advanced intermediates for archazolid A and B, (+)-discodermolide and (—)-callystatin A) are prepared from 1-haloalkyne via hydroboration-migratory insertion-Zn-promoted iodinolysis-Pd-catalyzed organozinc cross-coupling (eq 27). ... 

Table 4.15 Relative reactivities and rate constants for the hydroboration with (9-BBN)2 of haloalkynes and their parent compounds in CCl at 25 °C [2]...

The kinetic results [2] for hydroboration of haloalkynes and their unsubstituted parent alkynes are shown in Table 4.15. 

The change in charge polarization across the C C reflected in the C NMR data for haloalkynes indicates that polarization decreases in the order I > Br > Cl. This results in an increase in the amount of negative charge or electron density at C-2 and decrease in that at C-1, as one proceeds from the iodo- to bromo- to the chloro-substituted compounds. This thus correlates with the rate of hydroboration (which occurs at C-1) in the order I > Br > Cl. Further, the reason for the nucleophilic attack at the C-2 position [23] in 1-chloro-l-alkynes is the decrease in the electron density at that position caused by the -M effect of chlorine. Both regioselectivity and rate of hydroboration depend on the electron availability at specific sites in the molecule, and the above reason explains why hydroboration does not occur at the 2 position. 

The comparative data of C NMRfor 1-hexyne and the 1-halo-l-hexyne describe the importance of the -M effect, which in haloalkynes decreases in the order I > Br > Cl. In fluoroalkynes, no -M effect is possible as no d orbitals are available. Only a +M interaction is possible in the 1-fluoro-l-alkynes, and one expects their hydroboration at the C-1 position would (1) proceed at a slower rate than the corresponding chloro analogs, or (2) switch to C-2 position in case the electron density at C-1 decreases enough. Indeed, in 1-fluoro-l-alkynes the nucleophilic attack occurs at the C-1 position, whereas the same occurs at C-2 position in 1-chloro-1 alkynes [22a]. Their comparative hydroboration studies are not conducted [21], as fluoroalkynes are difficult to prepare and handle, and often very unstable [22]. 

Unlike 1-alkynes, the hydroboration of 1-haloalkynes with 1 equiv of 9-BBN or ChXjBH does not produce any dibora adducts Moreover, the hydroboration of 1-halo-1-alkynes with these reagents yields exclusively C-1 monohydrobora-tion products. The C-1 monohydroboration products are easily protonolyzed [26] with AcOH to give (Z)-l-halo-l-alkene (Eq. 24.13). 

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