Cyclopropane alkoxy

Non-heteroatom-stabilised Fischer carbene complexes also react with alkenes to give mixtures of olefin metathesis products and cyclopropane derivatives which are frequently the minor reaction products [19]. Furthermore, non-heteroatom-stabilised vinylcarbene complexes, generated in situ by reaction of an alkoxy- or aminocarbene complex with an alkyne, are able to react with different types of alkenes in an intramolecular or intermolecular process to produce bicyclic compounds containing a cyclopropane ring [20]. 

Asymmetric versions of the cyclopropanation reaction of electron-deficient olefins using chirally modified Fischer carbene complexes, prepared by exchange of CO ligands with chiral bisphosphites [21a] or phosphines [21b], have been tested. However, the asymmetric inductions are rather modest [21a] or not quantified (only the observation that the cyclopropane is optically active is reported) [21b]. Much better facial selectivities are reached in the cyclopropanation of enantiopure alkenyl oxazolines with aryl- or alkyl-substituted alkoxy-carbene complexes of chromium [22] (Scheme 5). 

Alkoxycarbene complexes with unsaturation in the alkyl side chain rather than the alkoxy chain underwent similar intramolecular photoreactions (Eqs. 10 and 11) [60]. Cyclopropyl carbene complexes underwent a facile vinyl-cyclopropane rearrangement, presumably from the metal-bound ketene intermediate (Eqs. 12 and 13) [61]. A cycloheptatriene carbene complex underwent a related [6+2] cycloaddition (Eq. 14) [62]. 

Scheme 10.12 gives some examples of enantioselective cyclopropanations. Entry 1 uses the W.s-/-butyloxazoline (BOX) catalyst. The catalytic cyclopropanation in Entry 2 achieves both stereo- and enantioselectivity. The electronic effect of the catalysts (see p. 926) directs the alkoxy-substituted ring trans to the ester substituent (87 13 ratio), and very high enantioselectivity was observed. Entry 3 also used the /-butyl -BOX catalyst. The product was used in an enantioselective synthesis of the alkaloid quebrachamine. Entry 4 is an example of enantioselective methylene transfer using the tartrate-derived dioxaborolane catalyst (see p. 920). Entry 5 used the Rh2[5(X)-MePY]4... 

The threo stereoisomer was the major product obtained by the synthesis in Scheme 13.14. This stereochemistry was established by the conjugate addition in Step A, where a significant (4-6 1) diastereoselectivity was observed. The C(4)-C(7) stereochemical relationship was retained through the remainder of the synthesis. The other special features of this synthesis are in Steps B and C. The mercuric acetate-mediated cyclopropane ring opening was facilitated by the alkoxy substituent.19 The reduction by NaBH4 accomplished both demercuration and reduction of the aldehyde group. 

Some remarks concerning the scope of the cobalt chelate catalysts 207 seem appropriate. Terminal double bonds in conjugation with vinyl, aryl and alkoxy-carbonyl groups are cyclopropanated selectively. No such reaction occurs with alkyl-substituted and cyclic olefins, cyclic and sterically hindered acyclic 1,3-dienes, vinyl ethers, allenes and phenylacetylene95). The cyclopropanation of electron-poor alkenes such as acrylonitrile and ethyl acrylate (optical yield in the presence of 207a r 33%) with ethyl diazoacetate deserve notice, as these components usually... 

In addition to siloxy- and alkoxy-substituted VCPs, alkyl- and H-substituted VCPs are also effective in the intermolecular [5 + 2]-cycloaddition reaction (Scheme 11). In general, an increase in the steric bulk of the cyclopropane substituent (H vs. Me vs. Pr1) leads to increased reaction rates, putatively through preferential population of the more reactive as-oid arrangement of the vinyl and cyclopropane moieties.43... 

Lithium tributylmagnesate induced iodine-magnesium exchange reaction of 5-alkoxy-3-iodomethyl-l-oxacyclopentanes (Scheme 16). A following intramolecular nucleophilic substitution led to construction of a cyclopropane with concomitant opening of the oxa-cyclopentane ring. 

Functionalized zinc carbenoids have been prepared from carbonyl compounds by an indirect strategy. The deoxygenation of a carbonyl compound to an organozinc carbenoid can be induced by a reaction with zinc and TMSCl. Therefore, the aldehyde or ketone, when treated with TMSCl or l,2-bis(chlorodimethylsilyl)ethane in the presence of an alkene, generates the cyclopropanation product. This method is quite effective for the production of alkoxy-substituted cyclopropane derivatives. A 55% yield of the... 

Another example of the superiority of the alkoxy group as a directing group was reported by Johnson in his synthesis of enantiomericaUy pure cyclopropyl ketones after auxiliary cleavage (equation 56). In that case, the product resulting from a sulfoximine directed cyclopropanation was never observed. 

The model involving the minimization of the A-1,3 ally lie strain followed by an alkoxy-directed cyclopropanation is quite reliable to predict the sense of induction in the cyclopropanation of chiral acyclic allylic alcohols. However, the application of this model is not as straightforward in the case of allylic ethers. Indeed, it was shown that the cyclopropanation of benzyl ethers led to a major anti or syn isomer depending upon the nature of the substituents (equation 67). ... 

An alkoxy group at the -position induces a cyclopropanation reaction of the dimetallic species as shown in equation 46. The formation of the gem-dimetal species proceeded diastereoselectively as described above. The ring closure proceeds with inversion of configuration to form stereospecifically the cyclopropane ring. An alkoxy substituent at the -position of the allylzinc reagent also induces the cyclopropanation reaction (equation 47)61a 72. 

In 1977, an article from the authors laboratories [9] reported an TiCV mediated coupling reaction of 1-alkoxy-l-siloxy-cyclopropane with aldehydes (Scheme 1), in which the intermediate formation of a titanium homoenolate (path b) was postulated instead of a then-more-likely Friedel-Crafts-like mechanism (path a). This finding some years later led to the isolation of the first stable metal homoenolate [10] that exhibits considerable nucleophilic reactivity toward (external) electrophiles. Although the metal-carbon bond in this titanium complex is essentially covalent, such titanium species underwent ready nucleophilic addition onto carbonyl compounds to give 4-hydroxy esters in good yield. Since then a number of characterizable metal homoenolates have been prepared from siloxycyclopropanes [11], The repertoire of metal homoenolate reactions now covers most of the standard reaction types ranging from simple... 

The carbenoid from Et2Zn/CH2I2 [17], particularly when generated in the presence of oxygen [18], is more reactive than the conventional Simmons-Smith reagents. The milder conditions required are suitable for the preparation of 1-[16, 19] or 2-alkoxy-l-siloxycyclopropanes [20], which are generally more sensitive than the parent alkyl substituted siloxycyclopropanes (Table 2). Cyclopropanation of silyl ketene acetals is not completely stereospecific, since isomerization of the double bond in the starting material competes with the cyclopropanation [19]. 

Table 2. Alkoxy siloxy cyclopropanes prepared by Et2Zn/CH2I2.

Isotopic labelling, Eq. (49), indicated that the transmetalation occurs via direct tin-carbon bond cleavage rather than via intermediate formation of an alkoxy-cyclopropane [45],... 

Scheme 5 summarizes the regiochemistry of ring opening of methyl- (6) and phenyl-substituted alkoxy-siloxy-cyclopropane (7) by LiOMe, ZnCl2, HgCl2) and TiCl4, as well as the 13C NMR chemical shifts of the respective metal methyls [27]. The NMR data correlate with the nature of the metal-carbon bond The more polarized it is, the less positive the chemical shift of the methyl group. 

I. From Aldehydes and Ketones with 1-Alkoxy-l-lithiocyclopropanes and from Enol Ethers by Cyclopropanation... 

Epoxides such as 10 can be prepared in high enantiomeric purity, by, inter alia, kinetic resolution. David Hodgson of Oxford University has demonstrated (J. Am. Chem. Soc. 2004, /26,8664) that on exposure to LTMP, monosubstituted epoxides are smoothly converted into the corresponding alkoxy carbenc or alkoxy carbenoid. When an alkene is available for insertion, the cyclopropane, in this case 11, is formed with high diastereocontrol. This represents a powerful new approach to enantioselective ring construction. It is possible that in the absence of a target alkene, the intermediate alkoxy carbene could divert to intramolecular C-H insertion, which might also proceed with substantial diastereocontrol. 

From the correspondingly substituted A -pyrazolines (18), 1-alkoxy- and l-acetoxy-l,2,2,3,3-pentasubstituted cyclopropanes were obtained in good yields by thermolysis in cyclohexane solution under nitrogen using a high-pressure vessel (91JHC1773). 

Up-to-date structural data on simple alkoxy and alkylthio cyclopropanes are scarcely available. 

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