Simmons-Smith reagent, synthesis

Gem-dibromospiropentane (620), obtained by the reaction of MCP with dibromocarbene, was used in the synthesis of BCP (3) (Scheme 90) [6a]. The reaction of the intermediate vinylidenecyclopropane 621 with a large excess of Simmons-Smith reagent gave exclusively BCP (3), but using modified Simmons-Smith procedures the [3]-triangulane (247) was also obtained in small yield (Scheme 91) [165],... 

SAMPLE SOLUTION (a) In a cyclopropane synthesis using the Simmons-Smith reagent, you should remember that a CH2 unit is transferred. Therefore, retro-synthetically disconnect the bonds to a CH2 group of a three-membered ring to identify the starting alkene. 

The Simmons-Smith reagent (4-33), other carbenoids, and carbenes are very useful in the synthesis of cyclopropanes (see Example 4.25). 

Cohen has used a soluble version of the Simmons-Smith reagent to promote the 3,2-rearrangement of allylic sulfides (Scheme 52). He has also applied this methodology to the synthesis of sarkomycin (225). The allylic sulfide (221), easily available via a Petrow reaction, was first alkylated and the sulfo-nium ylide was then generated by a fluoride-promoted desilylation. Rearrangement of the ylide (223) gave the homoallylic sulfide (224) which was eventually transformed into sarkomycin (Scheme 53). 

The classical Simmons-Smith reagent was used to cyclopropanate a double bond in the presence of a triple bond in the synthesis of racemic 11,12-cyclopropyl analogs of hepoxilins Aj and ( )-Undec-2-en-5-ynol (4) was treated with diiodomethane/zinc-copper couple in anhydrous diethyl ether to afford the intermediate racemic (lS, 2S )-l-hydroxymethyl-2-... 

This sequence has been used for the synthesis of the sesquiterpenes ( —)- and ( + )-thujop-sene. The allylic /1-hydroxysulfoximines 47 and 49 were separated by column chromatography on silica gel and treated separately with excess of Simmons Smith reagent prepared from zinc/ silver amalgam and diiodomethane in diethyl ether giving 48 and 50, respectively. The Simmons-Smith reaction took place stereospecifically cis to the hydroxy group of the allylic ff-hydroxysulfoximines. Cyclopropanes 48 and 50 were converted to ( —)- and (- -)-thujopsene. 

A new angular methylation procedure, at Cis, involving the Simmons-Smith reagent was discovered, thus extending the usefulness of the Smith-Torgov total synthesis of 19-norsteroids. The preparation and properties of 5,19-cyclosteroids was the subject of several studies.Interestingly enough, the Villsmeier reaction on enamines of 3-heto-A -steroids led to the 1,6-diformyl derivatives. ... 

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. 

Syntex workers7 later found that (3) can be dehydrogenated to (5) directly by DDQ in 90% yield (2.5 moles of DDQ, refluxing dioxane, 1-2 hrs.). This oxidation of an unactivated disubstituted olefin to a diene is rare a related reaction to the oxidation of tetramethylethylene to 2,3-dimethylbutadiene (2, 117). They then found that it was possible to shorten the original synthesis even further. Reaction of (1) with a modified Simmons-Smith reagent (this volume) gave (3) directly in 50% yield. The overall yield of (5) from naphthalene is thus about 40%. 

The last example shows an application of the cyclopropanation reaction in one step of a synthesis of 13,14-dihydro-13,14-methylene derivatives ofPGp2 and of PGE2. Cyclopropanation with the Simmons-Smith reagent failed in this case. 

The synthesis of the steroidal 2a,3a-cyclopropanol (137b) has been described. The 3-bis-(2-chloroethoxy)-derivative (135) was pyrolysed in vacuo to give the olefin (136). This with excess Simmons-Smith reagent gave the cyclopropyl steroid (137a), which with butyl-lithium liberated the free cyclopropanol (137b) this was converted into 17j8-hydroxy-2a-methyl-5a-androstan-3-one (138) by base. 

Simmons-Smith reagent ICLLZnI. a carbenoid used in cyclopropane synthesis from alkenes. 

Ring expansion induced by FeCla has been used in a new synthesis of dl-muscone in 237> overall yield from dimethyl tetradecanedioate, which was converted into (6) by the procedure of Ruhimann (4, 537). In this case cyclo-propanation with methylene iodide and diethylzinc (4, 153) proved superior to the Simmons-Smith reagent. ... 

Another interesting feature of this synthesis is the ring expansion used in sequences A and F. Trimethylsilyl enol ethers are treated with Simmons-Smith reagent to form cyclopropyl silyl ethers. These rings undergo oxidative cleavage and ring expansion when treated with... 

Organozinc compounds, XZnCRR (RR = H, alkyl, X halogen), are widely used for the synthesis of cyclopropanes as Simmon-Smith reagents [12,36,37,79- 93]. Simmon-Smith reagents are prepared by two processes as shown in eqs. (5.32) and (5.53). The first one is the reaction of diazomethane with zinc halides. The second is the reaction of methylene iodide with an activated zinc. Zinc containing 10% of... 

A rather unusual synthesis of spiro[2.3]hexanols (244) consists of treatment of the tertiary propargylic alcohols (243, R ,R = Me, Et, or Ph) with the Simmons-Smith reagent. ... 

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). 

In another route to cyclopropanes, diiodomethane is treated with zinc powder (usually activated with copper) to generate ICH2ZnI, called the Simmons-Smith reagent This species is an example of a carbenoid, or carbene-like substance, because, like carbenes, it also converts alkenes into cyclopropanes stereospecifically. Use of the Simmons-Smith reagent in cyclopropane synthesis avoids the hazards associated with diazomethane preparation. 

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