Addition 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... 

Many other 1,3-dipolar cycloadditions are known, amongst which is the addition of diazomethane (CH2N2). Expulsion of nitrogen from the adduct leads to the formation of a cyclopropane ring. Another way of achieving the same result involves the addition of a carbene such as the Simmons Smith reagent. This is generated from methylene iodide (CHjIj) and a zinc/copper couple. 

Steric course. Cyclopropane formation with the Simmons-Smith reagent is a stereospecific cis- addition for example cis- and tran.s-hexene-3 give pure cis- and fran5--l, 2-diethylcyclopropane. 

Acetylene additions Aluminum chloride. Dimethylsilylazine. Simmons-Smith reagent Thiolacetic acid. Zinc iodide (catalyst). 

In contrast to the addition of diazomethane to the norbornene double bond of endo- and exo-tricyclo[5.2.1.0 ]deca-3,8-diene vide supra), the Simmons-Smith reagent prepared from diiodomethane in the presence of zinc-silver couple undergoes nonseiective addition at both double bonds giving monocyclopropanated products at both positions in addition to the dicy-clopropanated products. 

An earlier successful attempt at asymmetric cyclopropanation was the addition of excess Simmons-Smith reagent to chiral allylic -hydroxysulfoximines prepared by the addition of (- -)-(5)-A,5 -dimethyl-5-phenylsulfoximine as its lithium derivative to ( + )-4a,8,8-trimethyl-4,4a,5,6,7,8-hexahydronaphthalen-2(3//)-one. ... 

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. 

Scheme 6.26. Auxiliary-based asymmetric cyclopropanations (addition of CH2 ) of a, 3-unsaturated aldehydes and ketones, (a) [98] (b) [99,100] (c) [101-104] (d) Proposed transition structures [104]. Only one zinc and the transfer methylene are shown other atoms associated with the Simmons-Smith reagent are deleted for clarity.

Diketones. Simmons-Smith reagent reacts with acid chlorides to afford the 1,3-diones. By addition of tetrahydrothiophene the monomeric form is stabilized. 

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. 

The effect of 3a- and 3/5-hydroxy-, 3a- and 3j8-acetoxy-, 3-ethylene ketal and 3a-methoxy-derivatives of cholest-5-ene on the addition of the Simmons-Smith reagent has been investigated. The addition of the reagent occurred only with epi-cholesterol (312) to give mainly 3a-hydroxy-5,6a-cyclopropano-5a-cholestane (313) (see Chapter 1, refs. 153—155). 

Scheme 8.80. A representation of the pathway from the f-butyldimethylsilyl ether of the enol of cyclohexanone to 2-methylcyclohexanone via the addition of methylene from the Simmons-Smith reagent and rearrangement of the cyclopropane formed (see Simmons, H. E. Smith, R. D. J. Am. Chem. Soc., 1959,81,4256).

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. 

General Methods.—The preparation of cyclopropanes by addition of the Simmons-Smith reagent [from CHjla + Zn (Cu)] to olefinic substrates has been a cornerstone in synthesis for almost two decades. Kawabata and co-workers have now described a seemingly more convenient procedure which uses copper in place of the familiar zinc-copper couple and produces cyclopropanes in comparable yields. In addition, the procedure can be employed with trihalogenomethanes and dibromo-acetates leading to monohalogenocyclopropanes and cyclopropane carboxylates, respectively, both with 5> n-stereoselectivity (Scheme 2). 

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. 

---