Addition reactions Simmons-Smith reagent

Aminocyclopropanes were prepared from enamines by the addition of Simmons-Smith reagent (688) or best through the cuprous-chloride-promoted decomposition of diazomethane (689). The reaction of an enamine with chloroform and base and opening of the resultant aminocyclopropane to an ynamine was reported (690). 

The esters, 7-ethoxycyclopropyl acetate (7 a) and benzoate (7b) have been synthesized by the addition of the Simmons-Smith reagent 22> to 1-ethoxy vinyl acetate and benzoate, respectively.4) A potential difficulty in this reaction lies in the fact that zinc iodide, a Lewis acid, is generated in the process and may induce cyclopropane ring opening (Section 4.3.3). However, when glyme is used as a solvent, the acid-labile bonds remain intact since the zinc salt is insoluble in this medium.23)... 

Similarly, the addition of the Simmons-Smith reagent (CH2I2 + Cu-Zn couple) to 1-ethoxyvinylacetate (or benzoate) provided 1-ethoxycyclopropylacetate, which upon reaction with methanol or ethanol yielded 3 or the corresponding methyl hemiacetal12). 

A cis addition mechanism is generally accepted for the reaction, because cis addition to an olefinic bond generally occurs with predominant attack at trans bonds, and the Simmons-Smith reagent attacks preferentially one of the trans olefinic bonds of trans,trans,cis-1,5,9-cyclodode-catriene and then the cis double bond of the monoadduct (378). The close correspondence in relative rates of olefins for the cyclopropane formation by the Simmons-Smith reaction with those for diimide reduction and peroxide epoxidation supports the concept 409). The latter two reactions are generally considered to proceed via cis addition. 

The Simmons-Smith reaction with allyl alcohol was reported to give dicyclopropylcarbinoxymethane (XXIX) in addition to cyclopropylcarbinol 307). This reaction is a useful one-step route to dicyclopropyl-carbinoxymethanes. Reaction of the Simmons-Smith reagent with... 

Methylene ( CH2) addition to a double bond has been achieved by use of the Simmons-Smith reagent (CH2I2 and a zinc-copper couple) f 70J. The reaction gives a cyclopropane derivative by stereospecific cis addition, and in allylic or homo-allylic alcohols leads to methylene addition ci to the hydroxyl function. Examples in the steroid field include a s-methylene addition to the double bonds of the ga-hydrdxy-A dO), 3j8-hydroxy-AJ- and 3 a- and 3/9-hydroxy-A4 systems... 

Decarbonylation of cyclopropene acids. In a study of the synthesis of methyl sterculate (6) from methyl stearolate (1), Gensler et al.1 were unable to repeat the apparently straightforward synthesis based on addition of the Simmons-Smith reagent described in 1, 1021-1022. They were also unable to eifect addition of methylene generated by cuprous bromide decomposition of diazomethane. However, the reaction of (1) with diazoacetic ester in the presence of copper bronze, followed by hydrolysis, gives the cyclopropene diacid (2) in 70-90% yield. 

No matter how they are generated, carbenes and carbenoids undergo four typical reactions. The most widely used reaction is cyclopropanation, or addition to a TT bond. The mechanism is a concerted [2 + 1] cycloaddition (see Chapter 4). The carbenes derived from chloroform and bromoform can be used to add CX2 to a 7T bond to give a dihalocyclopropane, while the Simmons-Smith reagent adds CH2. Carbenoids generated from diazoalkanes with catalytic Rh(II) or Cu(II) also undergo cyclopropanations. 

Carbenoid species, such as the Simmons-Smith reagent (Eq. 10.55), undergo facile additions to alkenes to create cyclopropanes. The reactions are stereospecific, making carbenoids synthetically useful versions of carbenes. Carbenoid compounds do not normally perform insertion reactions. 

Cyclopropyl ketones can be synthesized directly from silyl enol ethers by addition of acid chlorides to a reaction mixture of Simmons-Smith reagent and the enol ether (Scheme 3). In this reaction, the Znl by-product of the cyclopropanation sequence acts as a Friedel-Crafts type catalyst to activate the acid chloride. In related studies, Grignon-Dubois and co-workers have shown that the Friedel-Crafts acylation of cyclopropyltrimethylsilanes also provides an expeditious route to cyclopropyl ketones. 

In Summary Diazomethane is a useful synthetic intermediate as a methylene source for forming cyclopropanes from alkenes. Halogenated carbenes, which are formed by dehydro-halogenation of halomethanes, and the Simmons-Smith reagent, a carbenoid arising from the reaction of diiodomethane with zinc, also convert alkenes into cyclopropanes. Additions of carbenes to alkenes differ from other addition processes because a single carbon atom becomes bonded to both alkene carbons. 

Finally, it should be mentioned that from a purely synthetic point of view the reactions involving "transfer" of methylene groups -like the Simmons-Smith reaction [27] or Seyferth s reagents [28]- may be considered formally as cheletropic additions of a [2 + 1] type. 

The chemical behavior of heteroatom-substituted vinylcarbene complexes is similar to that of a,(3-unsaturated carbonyl compounds (Figure 2.17) [206]. It is possible to perform Michael additions [217,230], 1,4-addition of cuprates [151], additions of nucleophilic radicals [231], 1,3-dipolar cycloadditions [232,233], inter-[234-241] or intramolecular [220,242] Diels-Alder reactions, as well as Simmons-Smith- [243], sulfur ylide- [244] or diazomethane-mediated [151] cyclopropanati-ons of the vinylcarbene C-C double bond. The treatment of arylcarbene complexes with organolithium reagents ean lead via conjugate addition to substituted 1,4-cyclohexadien-6-ylidene complexes [245]. 

Dihalocydopropanes readily undergo reductive dehalogenation under a variety of conditions. Suitable choice of reagents and reaction conditions will allow the synthesis of monohalocyclopropanes or the parent cyclopropanes.19 " The ease of reduction follows the expected order I > Br > Cl > F. In general, complete reduction of dibromo and dichloro compounds is accomplished by alkali metal in alcohol,99-102 liquid ammonia103 or tetrahydrofuran (equations 28 and 29).104 The dihalocydopropanes can be reduced conveniently with LAH (equation 30).105 LAH reduction is particularly suited for difluoro compounds which are resistant to dissolving metal reductions.19 106 It is noteworthy that the sequence of dihalocar-bene addition to an alkene followed by the reduction of the dihalocyclopropyl compounds (equation 31) provides a convenient and powerful alternative to Simmons-Smith cyclopropanation, which is not always reliable. 

Cyclopropanes are commonly synthesized with Zn(CH2I)2 (37) using the Simmons-Smith-reactum.16 This reaction proceeds via one-step addition of one of the methylene groups of the zinc reagent to olefins. As an advantage of the Simmons-Smith-reaction no free carbene is involved. 

It is advantageous to utilize either titanium isopropoxide or trimethylaluminum complexes with aldehydes in general, because pinacol-coupled diols form with the Zn/CH2Br2/riG4 systems as minor side products. No evidence of Simmons-Smith-type side products was observed with any of the methylena-tion reagents. Additional examples of the reaction with aldehydes are presented in Table 11. 

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