Hydrozirconation of alkynes

The hydrozirconation reaction of alkynes tolerates the presence of a large variety of functional groups. As a consequence, this protocol has become very popular in organic synthesis [135-142]. 

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As for alkenes, the rate of hydrozirconation of alkynes decreases with increasing substitution on the alkyne. An unsymmetrical diyne reacts with 1 preferentially at the less-substituted triple bond [85]. 

The synthetic potential of alkenylzirconium complexes is partially due to the fact that the hydrozirconation of alkynes can be carried out in the presence of some synthetically useful functional groups such as halide [80,153, 211, 212], acetals, amides, imides, carbamates, sulfides [186], ester, cyano [95, 213] and chiral propargyl amino functionalities [214]. 

Hydrozirconation of alkynes with the Schwartz reagent, Cp2Zr(H)Cl (6), and subsequent methylation is also a general method (Eq. 2.5) [16]. 

Similarly, alkenylzirconium species prepared by the hydrozirconation of alkynes add in a conjugated fashion to enones. Formation of an intermediate zincate prior to transmetalation to the copper species facilitates the Michael addition (Scheme 2.62) [135]. This methodology has been applied to the preparation of protected misoprostol 129 (Scheme 2.63) [136, 137]. 

Hydrozirconation of alkyne 14, followed by cuprate addition, was then used to install the Cl3 20 side chain of 15. Reduction of the ketone (L-selectride) followed by hydrogen fluoride cleavage provides the F-series derivatives 16, while direct cleavage of 15 gave the E-series compounds 17. 

The kinetic product distribution can be further shifted in excess reagent to get organozirconium derivatives with high regioselectivity. Even subtle steric differences such as in 2-pentyne ensure high selectivity [Eq. (6.77), a]. As Eq. (6.77) demonstrates, hydrozirconation of alkynes is an exclusive syn process. 

The hydrozirconation of alkynes is a well-established reaction, giving vinylic zirconium species of known regio-and stereochemistry.176 These species react with aryltellurium halides leading to vinylic tellurides with the ( )-stereochemistry 98 (Scheme 61),177,178 so complementing the other general routes to these compounds which give preferentially the (Z)-products (Sections 9.13.5.2.3, 9.13.5.2.5). 

Hydrozirconation of alkynes with the Schwartz reagent Cp2Zr(H)Cl yields the chlorovinyl zirconocene 17, which is easily converted to the methyl vinyl zirconocene 18 with either methyllithium in THF or methylmagnesium bromide in CH2C12. Compound 18 loses further methane at room temperature to form a zirconacyclopropene intermediate 19, which couples with a second alkyne and forms the metallacyclopentadiene 20 (Scheme 6) [34]. 

Dabdoud et al. have shown that the hydrozirconation of alkyn-l-ylbutyl selenides was complete with two equivalents of Cp2Zr(H)Cl. The nature of the products, formed after reaction with BuTeBr, is dependent on the substituent R [78] (Scheme 56, reaction 1). With R=Ph, the ketene butylselanyl(butyl-telluranyl)acetal was obtained exclusively. In the other cases (R = alkyl, MeOCH2), small amounts of (Rj-(2-butyltelluranyl)vinyl butyl selenides were also produced. The hydrozirconation of substituted acetylenic butyl selenides could be considered as a convenient approach for the synthesis of... 

The cationic zirconocene species which result from the hydrozirconation of alkynes or alkenes then treatment with AgC104 or AgAsFg are sufficiently Lewis acidic to form new carbon-carbon bonds with aldehydes [43]. Two-carbon and four-carbon homologation reactions have been reported as an extension of this reaction (Eqs 39-41). 

Alkynes are universally hydrozirconated as well the only failure in the literature is that of a perfluori-nated compound, C7Fi5(2sCH. Alkynes appear to be more reactive than alkenes, both by qualitative comparison and from the results on enynes (Table 6 also see Section 3.9.3.3.1), Furthermore, hydrozirconation of alkynes can compete with reduction of unsaturated functional groups such as nitriles and esters (Table 5), which is generally not true for alkenes. Dienes can be cleanly monohydrozirconated if one of the double bonds is terminal other cases are considered in Section 3.9.3.3.I. 

Table 5 Hydrozirconation of Alkynes with Functional Groups...

For acyclic alkenes, the facile rearrangement process obviates most possibilities of stereoselective transformation. The one exception is that of stereospecific isotopic labelling, for which hydrozirconation is a potentially powerful technique compounds of type Bu CHDCHDX (36), useful for NMR-based mechanistic studies, are conveniently obtained as in Scheme 9. This requires that four separate processes — hydrozirconation of alkyne, cleavage of alkeiiylzirconium, hydrozirconation of alkene and cleavage of alkylzirconium — all be completely stereospecific. 

Protonolysis can also be effected with weaker acids in some cases this may be essential. For example, hydrozirconation of alkynic alcohols Me(CH2)nC=C(CH2)mOH with 2 equiv. of (6), followed by hydrolysis with 2% aqueous NH4CI, affords the corresponding cis-alkenol in high yield and selectivity, whereas use of aqueous HCl causes both cis-trans isomerization and allylic rearrangement. Protonolysis by weak acid may be slow enough for other reactions to compete TBHP can be used as an oxidant (see below). 

Utilization of stereodefined alkenylalanes or alkenylzirconium reagents in palladium-catalyzed cross-coupling reactions greatly enhances the versatility of Negishi-type coupling reactions. These organometallics are readily available by hydroalumi-nation, carboalumination, and hydrozirconation of alkynes, respectively. 

Swanson, D. R Nguyen, T., Noda, Y., Negishi, E. A convenient procedure for hydrozirconation of alkynes with iso-BuZrCp2CI generated in situ by treatment of Cp2ZrCI2 with tert-butylmagnesium chloride. J. Org. Chem. 1991, 56, 2590-2591. 

The hydrozirconation of alkynes by Cp2ZrHCl has been studied in detail . The addition of Zr-H is uniquely cis, and in 1-alkynes the zirconium attaches to the terminal carbon atom with high regioselectivity ( 98%). The direction of cis-fi addition of Zr-H to internal alkynes is sensitive to the steric bulk of the two substituents of the alkyne and, in the absence of excess Zr-H, is subject to kinetic control. The presence of excess Zr-H results in rapid equilibration of the initial mixture. The results of some hydrozirconations of internal alkynes are shown in Table H. 

Alkenylzirconium reagents Hydrozirconation of alkynes with Cp ZifHlCl followed by reaction with iodonium salts constitutes a method for synthesis of styrenes and enynes. In the latter case it can be seen that zirconium prefers attachment to the heterosubstituted carbon atom therefore, 1,1-difiinctionalized 1-alkenes are readily prepared, including those pairing Si/Se and Te/Te. ... 

Acylations. Alkenylzirconocene chlorides that are generated from hydrozirconation of alkynes readily undergo copper-catalyzed acylations. Thus, enones containing tin and selenium substituents are available from alkynylstannanes and alkynylselenides, respectively. Alkenyl alkynyl ketones are obtained when the reaction is carried out under carbon monoxide with alkynyliodonium salts. ... 

Hydrozirconation of alkynes. The reagent (1) undergoes facile clr-addition... 

As mentioned earlier, hydrozirconation of internal alkenes gives terminal alkylzir-conium compounds. The isomerization occurs so quickly that no intermediates are observed. The mechanism of the reaction is a series of insertions and /8-hydride eliminations. Isomerization does not occur upon hydrozirconation of alkynes. 

Stoichiometric studies of M-H additions to alkynes also show mixed stereochemical results. The more common cw-addition is typified by the CO-promoted transformation of Cp2Nb(H)(RCECR) to ds-Cp2Nb(CO)(Ti -CR=CHR) [90]. In mononuclear systems where frans-additions have been found, radical-type mechanisms have been implicated [91] or cis/trans isomerization of the intermediate vinyl species [92] has been found. Although the intermediacy of alkyne complexes has not been established, Schwartz s hydrozirconation of alkynes [93] by Cp2ZrHCl represents a general entry to vinyl-metal species which can be transformed stereoselectively to alkenes, vinyl halides, and/or carboxylic acids. 

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