Furukawa cyclopropanation

Enol ethers may also be cyclopropanated using zinc carbenoids stereoselectively. Furukawa cyclopropanation of enol ether 32 proceeds with high stereoselection, and the obtained cyclopropyl ether 33 can be easily transformed into the enantiomerically pure cyclopropyl alcohol 35 [30]. In this case, high stereoselectivity is achieved by employing the chiral diol 36, which is not commercially available. Using the commercially available enantiopure diol 37, the level of stereoselectivity is significantly lower (Scheme 7). 

The possibility of a radical mechanism is supported by the observation of the accelerating effect of molecular oxygen on the cyclopropanation. Miyano et al. discovered that the addition of dioxygen accelerated the formation of the zinc carbenoid in the Furukawa procedure [24a, b]. The rate of this process was monitored by changes in the concentration of ethyl iodide, the by-product of reagent formation. Comparison of the reaction rate in the presence of oxygen with that in the... 

Tab. 3.5 Cyclopropanation of the chiral enol ethers 92-95 under Furukawa conditions...

Salaiin J (2000) Cyclopropane Derivates and their Diverse Biological Activities. 207 1-67 Samoson A, Tuherm T, Past J, Reinhold A, Anupold T, Heinmaa 1 (2005) New Horizons for Magic-Angle Spinning NMR. 246 15-31 Sanz-Cervera JF, see Williams RM (2000) 209 97-173 Sartor V, see Astruc D (2000) 210 229-259 Sato S,see Furukawa N (1999) 205 89-129 Saudan C,see Balzani V (2003) 228 159-191 Sauvage J-P, see Dietrich-Buchecker C (2005) 249 in press... 

SalaiinJ (2000) Cyclopropane Derivatesand their Diverse Biological Activities.207 1-67 Sanz-Cervera JF,see Williams RM (2000)209 97-173 Sartor V, see Astruc D (2000)210 229-259 Sato S, see Furukawa N (1999) 205 89-129... 

The use of iodoform as the reagent precursor under Furukawa s conditions gives rise to a more complex scenario, since the additional C—I bonds can further react with an ethylzinc species (equation 8)" . The reaction of the iodo-substituted zinc carbenoid with an alkene will generate an iodo-substituted cyclopropane, whereas that involving the gem-dizinc carbenoid will lead to a cyclopropylzinc product. The evidence for the formation of a. gem-dizinc carbenoid was obtained not only by the analysis of the cyclopropanation products but also by the formation of rfi-iodomethane upon quenching the reagent with D2O/DCI. 

The solution structure of the Furukawa reagent (EtZnCH2l) has been established by H and NMR as well . This reagent is in equilibrium with Et2Zn and Zn(CH2l)2 (equation 12), but it has a limited lifetime it will either undergo cyclopropanation or it will rearrange to PrZnI. 

The level of diastereoselection in the cyclopropanation of chiral acyclic E-aUylic alcohols is highly dependent upon the choice of the reagent, the stoichiometry and the solvent. Charette has shown that, with simple ii-substituted chiral allylic alcohols, the use of an excess of the Furukawa reagent in dichloromethane provided the highest syn stereocontrol (equation 59). ... 

Preparation of the Furukawa s reagent (EtZnCH2l) syn-diastereoselective cyclopropanation of chiral acyclic allylic alcohols16... 

Fig. 3.16. Two reactions that demonstrate the stereospecificity of n s-cycLopropanations with the Simmons-Smith reagent. In the first reaction the zinc carbenoid is produced according to the original method, and in the second it is produced by the Furukawa variant.

Asymmetric Simmons-Smith cyclopropanation using no covalent-bound auxiliary but a chiral catalyst have only been successful with allylic alcohols so far. Fujisawa had shown that allylic alcohols such as 38 are converted into the corresponding alcoholate by Et2Zn (1.1 equivalents) first [31]. Addition of diethyltartrate (1.1 equivalents) results in the formation of an intermediate 39, which is cyclopropanated under Furukawa conditions (Et2Zn + CH2I2) to give compound... 

Furukawa-Simmons-Smith-Reakt.), 848 f. (Sawada-Sim-mons-Smith-Reakt.) E17a, 362f. (Ar—CH = M 4- En), 932 (3-C1 —2-Ar—propen/R2BH 4-OH-) E17b, 1279 (1-S02-Ar - 1-H) E18, 832 (En 4- Carben) E19b, 204/206 (En 4- Carben) Cyclopropan-[Pg.607]

In 1992 Kobayashi et al. [47] reported the first catalytic and enantioselective cyclo-propanation using the Furukawa modification [48] of the Simmons-Smith reaction of allylic alcohols in the presence of a chiral bis(sulfonamide)-Zn complex, prepared in-situ from the bis(sulfonamide) 63 and diethylzinc. When cinnamyl alcohol 62 was treated with EtgZn (2 equiv.), CHgIg (3 equiv.), and the bis(sulfonamide) 63 (12 mol %) in dichloromethane at -23 °C, the corresponding cyclopropane 64 was obtained in 82 % yield with 76 % ee (Sch. 26). They proposed a transition state XXIII (Fig. 5) in which the chiral zinc complex interacts with the oxygen atom of the allylic alkoxide and the iodine atom of iodomethylzinc moiety. They also reported the use of the bis(sulfonamide)-alkylaluminum complex 65 as the Lewis acidic component catalyzing the Simmons-Smith reaction [49]. 

A number of modifications of the original Simmons-Smith cyclopropanation procedure have been reported. Furukawa s reagent, (iodomethyl)zinc derived from diethylzinc and diiodomethane, ° or its modification using chloroiodomethane instead of diiodomethane, ° allows more flexibility in the choice of solvent. The reagent is homogeneous and the cyclopropanation of olefins can be carried out in non-complexing solvents, such as dichloromethane or 1,2-dichloroethane, which greatly increase the reactivity of the zinc carbenoids. 

An alternative to the Simmons-Smith and Furukawa reagents is iodomethylzinc phenoxide, readily accessible by deprotonation of phenol with Et2Zn and subsequent metal-halogen exchange with CH2l2- An economically attractive method for cyclopropanation of alkenes is to use CH2Br2, which is considerably less expensive and easier to purify and store than CH2l2- ... 

Allylic alcohols undergo cyclopropanation faster than unfunctionalized alkenes, " and excellent diastereoselectivities have been observed in reactions of the Furukawa reagent with acyclic chiral allylic alcohols. ... 

Cyclopropanation from alkenes and carbenes with alkyl gem dihalides and Zn-Cu couple (Simmons-Smith) or Et2Zn (Furukawa) EtgAI (Yamamoto) or Sm (Molander) with high diastereoselectivity (see 1st edition). 

CyclopropanationJ The title compound, prepared from ArOH, Et2Zn, and CH2I2, is a modified Simmons-Smith reagent, with which alkenes are transformed into cyclopropanes in excellent yields (6 examples, 90-98%). In terms of reactivity, the zinc phenoxide is comparable to bis(chloromethyl)zinc, but more reactive than bis(iodomethyl)zinc and Furukawa s reagent. 

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