Esters hydrozirconation

The first example of a stable 1,1-bidentate Lewis acid based on boron and zirconium has been reported [35]. The synthesis of 22 is outlined in Scheme 7.12. Treatment of hex-l-yne with HBBr2 Me2S followed by conversion of the dibromoboronic ester to the corresponding alkenyl boronic acid and esterification with propane-1,3-diol provided the alkenyl boronic ester. Hydrozirconation of this compound with 3 equivalents of the Schwartz reagent, Cp2Zr(H)Cl [57], afforded the desired product 22 in 86% yield. 

Hydrozirconation of various alkenylboranes [118-121] and alkenylzinc halides [34] with 1 provides the corresponding 1,1-bimetalloalkanes, which can be selectively converted to functionalized organic compounds [122-125]. Interestingly, alkenylzinc halides (RCH=CHZnX) show remarkable chemoselectivity, and functional groups such as chloride, cyanide, or ester functionality are tolerated [126]. 

Hydrozirconation of terminal alkynes R-C=CH (R= aryl, alkyl) with 1 affords terminally ( )-Zr-substituted alkenes with high efficiency and excellent stereochemical and regiochemical control (>98%). These alkenylzirconocene complexes are of particular interest for synthetic use [136, 143, 144]. Moreover, beside the electropositive halogen sources [145] and heteroatom electrophiles [3] used in the pioneering studies to directly cleave the Zr-C bond, ( )-vinyl-Zr complexes were recently transformed into a number of other trans-functionalized alkenes such as ( )-vinyl-sul-fides[146], vinylic selenol esters [147], vinyl-sulfones [148], vinyl-iodonium [149], vinyl-(R0)2P(0) [150], and vinilic tellurides [143]. 

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]. 

Carboxylic acids can be protected as oxazolines [96, 105-107, 186, 191] or as ester functions. Alkynic esters such as silyl esters [153, 211], tert-butyl esters [216], and even benzyl esters [153, 211] have been successfully hydrozirconated when the reactive site was a terminal alkyne or vinyl group (Scheme 8-27). 

The alkenylboronic esters were synthesized according to a literature procedure [56], Hydrozirconation of alkenylboronic esters with zirconocene hydrochloride, Cp2Zr(H)Cl, prepared by Buchwald s procedure [57], took place smoothly in CH2C12, providing in each case the corresponding borazirconocene 1,1-alkane 18 [34], Addition of propargyl bromide and a catalytic amount of copper(I) cyanide was accompanied by the disappearance of the yellow color associated with these compounds and by carbon—carbon bond... 

It should be pointed out that, compared to a-bromoboronic esters, p-bromoboronic esters are much less stable. For instance, dibutyl (2-bromoethyl)boronate readily undergoes P-elimination, even under solvolytic conditions [87]. Therefore, the reaction of 18 with NBS also reaffirms the regioselectivity of the hydrozirconation step. The reaction is highly general and works equally well for the preparation of a-chloro- and a-iodoboronic... 

Remarkably, the hydrozirconation can be applied to functionalized alkenylzinc reagents bearing an ester, chloride, or cyano functionality (Scheme 7.37) [230], The functionalized bimetallic species 129c—e gave significantly lower yields (55—64%) but excellent stereoselectivities (>94% ( ) Scheme 7.39). Although the (E)/(Z) ratio was always reproducible,... 

Addition of Cp2Zr(H)Cl to an alkenylzinc hahde affords relatively unstable 1,1-bimetallics of Zn and Zr. Addition of an aldehyde or a ketone is a general way to synthesize ( )-alkenes. Remarkably, the hydrozirconation can be applied to functionahzed alkenylzinc reagents bearing an ester, chloride or cyano functionahty (equation 43). ... 

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. 

Similarly, alkynic esters have been successfully hydrozirconated (Table 5). HCsC(CH2)3C02Bu gave the alkenylzirconium product in much higher yield than the corresponding methyl ester, which exhibited carboxy reduction. Clearly the reactivities of the C C and ester groups are in close balance here, with steric factors sufficient to tip it towards the former. Hydrozirconation of an alkenic ester would not be expected to work well no example is reported. In the reaction of an enone with (6 equation 21) little if any hydrozirconation of the C =C bond occurs. ... 

Functional groups can be protected carboxylic acids as oxazolines or silyl esters and alcohols as THP derivatives or potassium alkoxides. In fact, it may not be necessary to protect alcohols at all just use two equivalents of reagent The first will deprotonate the alcohol to give an alkoxyzirconium complex, and the second can then hydrozirconate the C=C or C C bond (equation 23). Several examples are shown in Tables 3 and 5. The presence of such functional groups does frequently have regio-chemical consequences, as will be shown in the following section. 

Reductive deformylation of 71 then gave a 50% yield of pentanoate 72, which still required an additional carbon atom to obtain the required fragment. This homologation was then accomplished via reduction of ester 72 to the aldehyde, chain extension to the terminal dibromide, and conversion to the acetylene 73 (55%). Hydrozirconation followed by quenching with iodine afforded the desired fragment 74 in 67% yield. 

Hydrozirconation of alkenes as a route to rr-alkylzirconiums is limited by other reactive functional groups e.g., alkynes react more readily than alkenes with (/j -Cp)2ZrHCl, and other reactive functional groups with ( / -Cp)2ZrHCl include alcohols, aldehydes, ketones, carboxylic acids, carboxylic acid esters, nitriles and thiocarbonyls . Alcohols may be protected either as alkyl ethers or as trialkylsilyl ethers. 

After hydrozirconation with Cp2ZrEt2 and reaction with an chloroformic ester, alkynes directly (requiring no catalyst) afford conjugated esters. ... 

An even more striking reaction of the alkylzirconium compounds formed by hydrozirconation is insertion of carbon monoxide into the C—Zr bond to form zirconium-acyl complexes. For example, 1-hexene or an internal hexene is treated in benzene with (1) to form the alkylzirconium complex (6), which is then allowed to react under 20 psi of carbon monoxide at room temperature. The colorless acyl complex (7) is formed within several hours. An intermediate zirconium carbonyl species is not detected. The acyl complex (7) is converted into an aldehyde (8) on protonolysis, into a carboxylic acid (9) by treatment first with aqueous NaOH and then 30% H2O2, or into an ester (10) by treatment with NBS and then with an alcohol. This procedure differs significantly from... 

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