Simmons-Smith reaction intermediate

It is clear that free CH2 is not involved in the Simmons-Smith reaction, but there is substantial evidence to indicate that caibenes aie formed as intermediates in certain other reactions that convert alkenes to cyclopropanes. The most studied exanples of these reactions involve dichlorocaibene and dibromocaibene. 

Furthermore, cyclopropane structures have often served as intermediates in organic synthesis. For these reasons, olefin cyclopropanation has proved to be a useful tool for synthetic organic chemists. This has led to the development of several methods for cyclopropanation reactions,91 including the metal-catalyzed reactions of diazo compounds with olefins, as well as the Simmons-Smith reaction. 

Methylene can be transferred directly from the reagent mixture, CHjIj + Zn-Cu alloy, to the alkene without being generated as an intermediate (Simmons-Smith reaction). 

The intermediates in the Simmons-Smith reaction show much more controlled reactivity than, for example, diazoalkanes. Competing side reactions are greatly reduced, and insertion reactions are generally not seen. For example, the free hydroxy group is tolerated as indicated by the above discussion of directing effects. The reaction is also compatible with many other functional groups. 

Organomercury compounds such as ICFbHgl and Hg(CH2Br)2 may be prepared by the reaction of metallic mercury with diiodomethane or by reaction of mercury(II) salts with diazoalkanes. These mercury derivatives are related to the intermediate that has been proposed in the Simmons-Smith reaction, and likewise, they have been found to convert alkenes into cyclopropanes.92... 

There are many ways of generating what appear to be carbenes. But in some cases at least, it seems clear that no free carbene is actually an intermediate instead, a carbenoid (carbene-like) reagent transfers a carbene unit directly to a double bond. For example, in the extremely useful Simmons-Smith reaction... 

Normally the chiral auxiliaries are introduced and removed in the asymmetric synthesis of Simmons-Smith reactions of allylic alcohols to provide mostly /rani-disubstituted cyclopropanes. Stereoselective syntheses of c -disubstituted cyclopropanes are difficult to achieve. Starting from (Z)-3-phenylprop-2-en-l-ol (80a) and (Z)-6-phenylhex-2-en-l-ol (80b), the corresponding c -disubstituted cyclopropanes 81a and 81b were prepared by first treating them with diethylzinc followed by diethyl (- -)-(/ ,7 )-tartrate (DET). A zinc-bridged intermediate is assumed to be formed first. This is subsequently treated with diethylzine and diiodomethane to give the products 81. The reaction conducted at — 12 "C gave the cyclopropanated products 81a and 81b with 70 and 81% ee, respectively.This method has the advantages that the introduction of the chiral auxiliary to the substrate and its removal are not neccessary and that both cis- and trans-disubstituted cyclopropanes could be prepared from (Z)- and ( )-allylic alcohols, repectively. 

The Simmons-Smith reaction takes place via an intermediate organozinc species, which can be generated in the presence of chiral ligands for zinc. Alternatively, standard (achiral) zinc reagents can be used to cyclopropanate an alkene bearing a chiral residue. The reactions of allylic alcohols are rapid, and the forma-... 

The synthesis of Drospirenone 41 (Scheme 1-15) [83] starts with the inexpensive androstenolone 66, which can be converted microbiologically (Colletotrichum lini) into the 7a,15a-dihydroxy derivative 67. A selective epimerization at C(7) proceeds by way of the acetal 68. Methylenation of the intermediate (C=C) bond appearing between C(15) and C(16) is successfully accomplished with the aid of dimethylsulfoxonium methylide to provide 71, and that of the (C=C) bond between C(6) and C(7) through a Simmons-Smith reaction. The conversion of 76 into 41 can be carried out in a one-pot procedure, with a Pd-catalyzed hydrogenation being followed by a Ru-catalyzed oxidation and a hydrochloric acid-induced dehydration. 

The rhodium chemistry just presented actually involves C=Rh species rather than a free carbene. In this section, we will look at a general class of compounds called carbenoids. A carbenoid is a reactive intermediate that reacts similarly to a carbene but does not actually involve formation of a carbene. The most commonly used carbenoid is generated by reaction of diiodomethane and a Zn/Cu couple this reaction, when it adds to alkenes, is called the Simmons-Smith reaction.316 A simple example is the conversion of cyclohexene to bicyclo[4.1.0]heptane (norcarane, 336). Initial reaction of diiodomethane with zinc gave an iodozinc compound (399-see sec. 9.8.B for a brief discussion of organozinc compounds), which added to the alkene to give 400. Loss of zinc iodide (Znl2) gave the cyclopropane derivative (343 in this case).3ll A one-step... 

Carbenes ( CR2) are the most reactive organic intermediates. The Simmons-Smith reaction (see chapter 6) tamed the extraordinarily reactive methylene ( CH2) in the form of a metal-carbenoid ( ICH2ZnI ). In 1964, Ernest Otto Fischer made the first metallocarbenes [e.g., (C0)5W=CCH3(0CH3)] and they were stable enough for X-ray diffraction studies on crystalline samples. Although unsuspected at the time, metallo-carhenes would hold the secret to the magic of olefin metathesis. 

When the thioacetal (128) was treated with allylmagnesium bromide and subsequently with BFs etherate, nucleophilic addition on the carbonyl carbon and a subsequent cationic cyclization took place the product (129) was obtained by aromatization with loss of methanethiol (Scheme 18) <84TL5095>. The reaction of (128) under the Simmons-Smith reaction conditions gave the thienothiepine derivative (130). The proposed mechanism for the formation of (130) involves a nucleophilic attack of the initially formed sulfonium ylide intermediate, intramolecular aldol type condensation, aromatization and demethylation (Scheme 19) <89TL3093>. 

Gloss and Moss have suggested the term carhenoid to describe intermediates that exhibit reactions quahtatively similar to those of carbenes without necessarily being free divalent carbon species. When carbenes are coordinated with metals they are known as carbenoids that have modified reactivities. lodomethylzinc iodide is often referred to as a carhenoid, because it resembles a carbene in its chemical reactions (Simmons-Smith reaction) (Scheme 5.14). Rhodium and copper carbenoids are unstable whereas some transition metals such as tungsten and chromium form stable and isolable carbenoids called metallocarhenes or Fischer carbenes. Carbenoids are structurally related to singlet carbenes and possess similar reactivity. 

Cyclopropanation of alkenes, in both inter- and intramolecular modes, constitutes an attractive route to polycycloalkanes. These cyclopropanations of alkenes are carried out through car bene or carbenoid intermediates . For the direct cyclopropanation of alkenes, the methylene iodide zinc-copper couple (Simmons-Smith reaction)reagent is commonly used. Several modifications of this procedure, including acceleration with ultrasound, are known °°. A somewhat less frequently used procedure for cyclopropanation is through methylene addition from diazomethane, which can be carried out either thermally or photochemically or in the presence of metal salts, e.g. Pd(OAc)2 or Rh2(OAc)4. In Table some examples of the preparation of cyclopropane bearing... 

It was decided to give only a limited amount of information on the Reformatsky reaction (see Sect. 2.2) and not to deal at all with the Simmons-Smith reaction in which an intermediate carbenoid zinc reagent is involved [47] ... 

However, in 1958, yet another powerful synthetic tool in which zinc plays a major role, was introduced to organic chemists i.e. the Simmons-Smith reaction [44, 45]. In this procedure, use is made of a carbenoid intermediate, formed by interaction of the metal (most commonly a zinc/copper alloy is used for this reaction) with diiodomethane ... 

Cyclopropanes can be made stereoselecfively by the Simmons-Smith reaction. Diiodomethane, zinc and an alkene are heated together in ether. The intermediate is probably ICH Znl. 

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