Hydroboration of 1-halo-1-alkynes

The hydroboration of 1-halo-l-alkynes is a key step in the synthesis of trans-alkenes [18], tram,trans-dienes [19], and cis-l-halo-l-alkenes [20]. In contrast to the hydroboration of 1-alkynes, 9-BBN reacts with 1-halo-l-alkyne in an equimolar ratio, with monohydroboration occurring at the 1 position (Eq. 5.31) [21]. 

The relative reactivities of 1-halo-l-alkynes are summarized in Table 5.25 

The decrease in the rate is the order of Cl Br I, an expected induction trend of halogens. As the rate reduction in the largest halogen substituent, iodine, is the smallest, the electronic effects must outweigh the steric effects in the case of bromine and chlorine substituents. The results are summarized in Table 5.26 [21] and Chart 5.15. 

The change in charge polarization across the triple bond has been found to decrease in the order I Br Cl. This, thus, corresponds to an increase in the amount of negative charge or electron density at C-2 and decrease in that at C-1 by proceeding from the iodo- to the bromo- to the chloro-substituted compounds. These observations correlate with the rate of hydroboration with 9-BBN at C-1 in the order of I Br Cl. 

The sensitivity to a change in alkyl group is the lowest of iodoalkynes among its counterparts, bromoalkynes, and chloroalkynes (Chart 5.17). 

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Terminal and internal (Z)-l-alkenylboronates are prepared from (Z)-(haloalkenyl)boronic esters (4) which can be readily obtained by hydroboration of 1-halo-1-alkynes [15, 17, 18]. 

Terminal and internal (Z)-l-alkenylboronates are prepared from (Z)-(l-halo-l-alkenyl)boronates [23]. which can be readily obtained by hydroboration of 1-halo-1-alkynes (Scheme 16.2). The internal Sv,2-like displacement of the halogen with hydrides [24] or organolithiums [25] takes place wath complete inversion of configuration at the sp carbon. On the other hand, the palladium-catalyzed alkylation of the C—X bond with organozinc reagents provides ( )-l-alkenylboronates [26] which are not available by conventional hydroboration of internal alkynes. 

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). 

An alternative synthesis of (Z)-l-halo-l-alkenes involves hydroboration of 1-halo-l-alkynes, followed by protonolysis (246,247). Disubstituted ( )-and (Z)-a1keny1 bromides can be prepared from ( )- and (Z)-a1keny1 boronic esters, respectively, by treatment with bromine followed by base (248). 

The mildness of these reagents tolerates the presence of various functional groups such as ester, ether, halogen, and nitrile. The stereospecific cis nature of hydroboration gives exclusively the tram alkenylboranes, often also in high regioisomeric purity (Eq. 53). On the other hand, highly pure (Z)-l-alkenyl-dialkylboranes are prepared without any difficulty via the monohydroboration of 1-halo-1-alkynes with disiamyl-borane or dicyclohexylborane, followed by treatment with t-butyllithium (Eq. 55)106). 

CeUalytk effect The hydroboration of 1-halo-l-alkynes with 9-BBN is catalyzed... 

Alkylalkenylborane derivatives can be obtained by hydroboration of 1-halo-l-alkynes with dialkylboranes, followed by the base-induced migration of an alkyl group from boron to the adjacent carbon atom ° ... 

As mostly discussed earlier. Type III alkenyl derivatives, that is, ( )-R CH= CHM(or X), are widely and satisfactorily generated by (i) alkyne hydrometallation (M = B, Zr or, in some cases, Al, etc.) (Table 3.2, Scheme 3.6), (ii) polar halogenation reactions ofalkynes (Eqs. (1), (2), and (7), Scheme 3.15), and additionally, (iii) anti bromoboration of ethyne [53] followed by Negishi coupling (Eq. (1), Scheme 3.12). On the other hand. Type IV alkenyl derivatives may be prepared by (i) Normant alkylcupration of ethyne [67, 68] (Eqs. (5) and (6), Scheme 3.11), (ii) Zr-catalyzed alkylalumination of ethyne, (iii) syn hydroboration of 1-halo-l-alkynes followed by hydride-induced inversion of configuration [59] (Scheme 3.9), (iv) hydroboration of 1-alkynes followed by brominolysis (but not iodinolysis) with inversion [95], and (v) syn hydrozirconation or syn hydroalumination of 1-boryl- or 1-silyl-l-alkynes followed by protonolysis of the C-Al or C-Zr bond [96-98]. 

Table 5.25 Relative reactivities for the hydroboration with (9-BBN)2 of 1-halo-1-alkynes and their parent compounds in CCl at 25 °C [21]...

Excellent yields of stereochemically pure cw-alkenylboranes can be synthesized by the hydroboration of 1-halo-l-alkynes with dialkylboranes followed by treatment with t-butyl-lithium at —78 °C." A similar study reported a stereoselective... 

Both ( )- and (Z)-l-halo-l-alkenes can be prepared by hydroboration of 1-alkynes or 1-halo-l-alkynes followed by halogenation of the intermediate boronic esters (244,245). Differences in the addition—elimination mechanisms operating in these reactions lead to the opposite configurations of iodides as compared to bromides and chlorides. 

The ketones can also be prepared from 1-halo-l-alkynes. Dialkylboranes, generated in situ via hydridation of dialkylhaloboranes, hydroborate 1-bromo-l-alkynes to... 

A )-and (Z)-alkenylboranes, or the corresponding boronic esters or potassium tri-fluoroborates, are conveniently available via hydroboration of terminal alkynes or 1-halo-1-alkynes using either disiamylborane, dicyclohexylborane, dibromoborane dimethyl sulfide, or catecholborane as hydroborating agents. ... 

Syn hydroboration of internal alkynes tends to give a mixture of two possible regioisomers. In cases where 1-halo-l-alkynes are used as internal alkynes, the reaction is nearly 100% regioselective placing B at the halogen-bound carbon. The resultant (Z)-a-haloaIkenylboranes can be used to prepare (i) (Z)-l-alkenylboranes (Type IV) [59], (ii) (Z)-a,P-disubstituted alkenylboranes (Type V) [60], and (iii) ( )-a,P-disubstituted alkenylboranes (Type VI) [61] as summarized in Scheme 3.9. 

Unlike 1-alkynes, which give considerable amount of dihydroboration at the 1 position [1], the 1-halo-1-alkynes alford only monohydroborating products and hydroboration occurring at the 1 position (Eq. 4.17) [2]. 

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]. 

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