Zinc carbenoids preparation

In contrast to the extensive body of work on the preparation of these zinc carbenoids, few investigations are on record concerning the mechanism of the Furu-kawa method for carbenoid formation. Two limiting mechanisms can be envisioned - a concerted metathesis via a four-centered transition structure or a stepwise radical cleavage-recombination (Scheme 3.11). 

II. PREPARATION AND STRUCTURE OF ZINC CARBENOIDS A. Unsubstituted Halomethylzinc Carbenolds... 

Functionalized zinc carbenoids have been prepared from diiodoalkanes and diethylzinc and used in stereoselective transformations, but their use is limited by the availability of the diiodoalkane" ° and the stability of the resulting zinc carbenoid. Alternatively, the reaction of a diazoalkane with Znl2 can be used to access complex zinc carbenoids, but with modest efficiency (equation 9) . ... 

Functionalized zinc carbenoids have been prepared from carbonyl compounds by an indirect strategy. The deoxygenation of a carbonyl compound to an organozinc carbenoid can be induced by a reaction with zinc and TMSCl. Therefore, the aldehyde or ketone, when treated with TMSCl or l,2-bis(chlorodimethylsilyl)ethane in the presence of an alkene, generates the cyclopropanation product. This method is quite effective for the production of alkoxy-substituted cyclopropane derivatives. A 55% yield of the... 

The intramolecular version of the cyclopropanation of alkenes using zinc carbenoids has not been extensively studied. One major limitation is the need to prepare the precursor, since there are relatively few mild methods to generate 1,1-diiodoalkanes (equation 44) ". 

Two approaches allow for the preparation of enantiomericaUy enriched bicyclo[n, 1.0] systems using zinc carbenoids. The first, developed by Johnson, involves the directed... 

To solve this problem, the authors prepared the zinc carbenoid 15 via the corresponding lithium carbenoid which is known to be formed stereoselectively10 (method B, equation 8)9. 

The Simmons-Smith reaction is a powerful method for preparing cyclopropanes from olefins using zinc carbenoids (IZnCH2I, EtZnCH2I, Zn(CH2X)2).7a,278,278a A variety of versions of this reaction have been developed and new carbenoids species have been made. For recent reviews, see Ref 279 and 279a. 

Chiral homoallylic alcohols and amines were prepared by using a four-component condensation reaction based on a zinc homologation followed by a trapping with an aldehyde or an imine.301 A regio- and stereospecific carbocupration reaction on alkynyl sulfoxide provides the corresponding metallated /3,/3-dialkylated a,/ -ethylenic sufoxide 98. Addition of aldehydes or imines, followed by addition of the bis(iodomethyl)zinc carbenoid, provides adducts 99 in good overall yield and with very high diastereoselectivity (Scheme 36). 

Another approach in the preparation of zinc carbenoids has been developed by Wittig [16]. It involves the reaction of diazomethane with a Zn(II) salt, but the delicate preparation of diazocompounds has hindered the wide spread preparative application so far (scheme I). 

The formation of w-propyl and -butyl iodides is a side reaction in the preparation of cyclopropane derivatives from olefins by the reaction with diethylzinc and em-diiodoalkanes 163). This side reaction is enhanced by the presence of lithium or magnesium halides, and was explained in terms of insertion of the zinc carbenoid into the carbon-iodine bond 245). 

The more recently reported route to diethyl 3-oxoalkylhosphonates uses a zinc carbenoid-mediated approach, which is believed to proceed through the intermediacy of a cyclopropylzinc alkoxide. Thus, treatment of simple diethyl 2-oxoaIkylphosphonates with the Furukawa-modifled Simmons-Smith reagent provides a rapid and efficient preparation of 3-oxoalkyIphosphonates. The chain extension of simple, unfunctionalized P-ketophosphonates requires an excess (6 eq) of both Et2Zn and CH2I2 at room temperature. The presence of a-substitution on the 2-oxoalkylphosphonate does not diminish the efficiency of the reaction (see Section 7.2.3.7). 

Although the Simmons-Smith reaction has found considerable use in organic synthesis, it is not readily applicable to the formation of highly substituted cyclopropanes, since 1,1 -diiodoalkanes (other than diiodomethane) are not readily available. Substituted zinc carbenoids can be prepared from aryl or a,p-unsaturated aldehydes (or ketones) with zinc metal, and these species can be trapped with an alkene to give substituted cyclopropanes.The addition of chromium carbenes (see Section 1.2.2) to alkenes can be used to effect cyclopropanation to give substituted cyclopropanes. Thus, addition of excess 1-hexene to the chromium carbene 113 gave the cyclopropane 114 as a mixture of diastereomers, with the isomer 114 predominating (4.92). ... 

Scheme 4.15 Preparation of zinc carbenoids by iodine—zinc exchange reactions [83, 85].

This methodology was subsequently extended to the reaction with ketones, which allowed the diastereoselective preparation of adjacent quaternary aU-carbon stereogenic centers in an acyclic system [105]. In the case of ethoxyacetylene 360, the alkenylcopper derivatives 361 were formed quantitatively, followed by homologation with a zinc carbenoid and reaction of the resulting aUenylzinc intermediates with ketones (Scheme 10.124). 

The formation and control of chiral quaternary centers by multicomponent reactions is undoubtedly a challenging task. The combination of a carbometalation reaction of chiral alkynyl sulfoxide 33, followed by a zinc homologation and an allylation in a four-component process, allowed the preparation of homoallylic alcohols or amines 34 bearing tertiary and quaternary stereocenters in a single step with high yields and diastereoselectivities (Scheme 11.13). The zinc carbenoid used in this reaction can be prepared independently or in situ by the reaction of diethyl zinc and diiodomethane. This carbenoid readily homologates the vinyl copper into the allylic species, which reacted diastereoselectively with aldehydes, to give the expected products. The chiral sulfinyl moiety can be easily removed by treatment with alkyllithi-ums, which allows a further functionalization of the carbon skeleton [35]. 

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