Cyclopropanation with diazo compounds

Salomon RG, Kochi JK (1973) Copper(I) catalysis in cyclopropanations with diazo compounds. Role of olefin coordination, J Am Chem Soc 95 3300-3310... 

The rhodiumcarbene intermediate, which is believed to be the active species in rhodium acetate catalyzed cyclopropanations with diazo compounds, shows electrophilic reactivity. Thus, diazopropenes preferentially add to electron-rich alkenes, demonstrated by the reaction of 3-diazo-l,l-dichloropropene (15) with 2-trimethylsiloxybuta-l,3-diene (16) . A mixture of Z-configurated divinylcyclopropanes 17 and rearranged dienones 18 was obtained (see also Section 1. B.2.4.5.1. for further examples of the formation of seven-membered rings such as 18). 

The cyclopropanation with diazo compounds via decomposition is amenable to asymmetric induction using chiral metal chelates. Rhodium complexes of 3(S)-phthalimido-2-piperidinone and Al-(arenesulfonyl)proline 44 are typical. The latter catalyst is suitable for generating alkenylcarbenoids. For intramolecular reactions, the cognate complex 45 and the semicorrin-copper 46 are effective. 

Chiral cyclopropanes are important compounds found in biologically active molecules. As efficient synthesis for these compounds are in demand many asymmetric cyclopropanation methods have been developed. Among these, cyclopropanation with diazo compound decomposition is outstanding. 

Cyclopropanation with Diazo Compounds. Copper(I) triflate is a highly active catalyst for the cyclopropanation of alkenes with diazo compounds. In contrast to other more extensively ligated copper catalysts, e.g. copper(II) acetylacetonate, that favor cyclopropanation of the most highly substituted C=C bond. 

A successful tandem catalysis was found by Barluenga et al. [80]. In the presence of [Cu(CHjCN)4][BF ], vinyldiazoacetates 113 readily undergo a copper(I)-cata-lyzed cyclopropanation with diazo compounds 114 and a copper(I)-catalyzed ring expansion of the cyclopropane intermediate 115 to substituted cyclobutenes 116 (Scheme 5.77). Changing the diazo compounds 114 to iminoiodinanes 117 leads to substituted 2-azetines 118 (Scheme 5.78) [81]. As shown in Scheme 5.79, the process... 

Scheme 6.1 Catalytic cycle of metal-catalysed carbenoid cyclopropanation reactions with diazo compounds.

Since their first introduction by Brunner and McKervey as chiral catalysts for the asymmetric cyclopropanation of alkenes with diazo compounds, chiral dirhodium tetra(A-arylsulfonylprolinates) complexes have been widely used by Davies,in particular, in the context of these reactions. Therefore, the use of... 

The detailed mechanism of transition metal-catalyzed cyclopropanation using diazo compounds as a carbene source is still covered by clouds of controversy, but it is generally accepted that the reaction proceeds through metal-carbenoid complexes,17-21 and the valency of the metal ions (M) changes with carbenoid formation (Scheme 85). 

Doyle, M. P. McKervey, M. A. Ye, T. Modem Catalytic Methods for Organic Synthesis with Diazo Compounds From Cyclopropanes to Yelides ... 

The glyoxime-Co(II)-catalyzed asymmetric cyclopropanation shown in Scheme 94 is noteworthy (226). The results of the detailed kinetic study are consistent with the mechanism of Scheme 92, however, the intermediary Co carbenoid species has substantial radicaloid properties, and only styrene and other conjugated olefins can be used as substrates. Simple alkenes are not cyclopropanated by diazo compounds. The reaction of deuterated styrene proceeds in non-stereospecific manner without retention of geometrical integrity. 

The generation and addition of acyl- and alkoxycarbonylcarbenes to alkenes is usually carried out by using the corresponding diazo derivatives under catalysis of metallic compounds. The metal-catalyzed cyclopropanation reactions with diazo compounds are described in detail by McKervey in Chapter 11, hence dealt with rather briefly in this chapter. The readers who are interested in the preparation of acyl- and alkoxycarbonyl-substi-tuted cyclopropanes are requested to refer also to Chapter 9. 

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

The reaction of electron-rich alkenes with diazo compounds containing two electron-withdrawing groups does not always result in cyclopropane formation. Instead, a [3+2] cycloaddition can occur, presumably by means of a stepwise process [1,2]. One report has appeared which demonstrates that the N-amido-prolinate 3 can catalyze a [3+2] cycloaddition between diazocyclohexane-1,3-dione (39) and 2,3-dihydrofuran (40) to form the tricyclic system 41 with very high enantioselectivity [Eq. ( 21)] [8]. 

Doyle MP, McKervey MA, Ye T (1998) In Modern catalytic methods for organic synthesis with diazo compounds from cyclopropanes to ylides. Wiley, New York... 

Cyclopropanation reactions are one set in an array of C-C bond-forming transformations attributable to metal carbenes (Scheme 5.1) and are often mistakenly referred to by the nonspecific term carbenoid. Both cyclopropanation and cyclopropenation reactions, as well as the related aromatic cycloaddition process, occur by addition. Ylide formation is an association transformation, and insertion requires no further definition. All of these reactions occur with diazo compounds, preferably those with at least one attached carbonyl group. Several general reviews of diazo compounds and their reactions have been published recently and serve as valuable references to this rapidly expanding field [7-10]. The book by Doyle, McKervey, and Ye [7] provides an intensive and thorough overview of the field through 19% and part of 1997. 

TABLE S.3. Enantioselective Cyclopropanation of Alkenes with Diazo Compounds Catalyzed hy the Pfaltz Semicorrin Catalysts 4 and 5... 

Rh(II) carboxylates, especially Rh2(OAc)4> have emerged as the most generally effective catalysts for metal carbene transformations [7-10] and thus interest continues in the design and development of dirhodium(II) complexes that possess chiral51igands. They are structurally well-defined, with D2h symmetry [51] and axial coordination sites at which carbene formation occurs in reactions with diazo compounds. With chiral dirhodium(II) carboxylates the asymmetric center is located relatively far from the carbene center in the metal carbene intermediate. The first of these to be reported with applications to cyclopropanation reactions was developed by Brunner [52], who prepared 13 chiral dirhodium(II) tetrakis(car-boxylate) derivatives (16) from enantiomerically pure carboxylic acids RlR2R3CC OOH with substituents that were varied from H, Me, and Ph to OH, NHAc, and CF3. However, reactions performed between ethyl diazoacetate and styrene yielded cyclopropane products whose enantiopurities were less than 12% ee, a situation analogous to that encountered by Nozaki [2] in the first applications of chiral Schiff base-Cu(II) catalysts. 

Reactions of transition-metal coordinated olefins with diazo compounds as a route to cyclopropane products have not yet been rigorously established. Catalysts that should be effective in this pathway are those that are more susceptible to olefin coordination than to association with a diazo compound and also those whose coordinated alkene is sufficiently electrophilic to react with diazo compounds, especially diazomethane. Pd(II), Pt(II), and Co(II) compounds appear to be capable of olefin coordination-induced cyclopropanation reactions, but further investigations will be required to unravel this mechanistic possibility. 

Due to the electrophilic character of carbenes. they are not expected to easily react with electron-poor alkenes, and the only reported examples concern reactions with diazo compounds (i.e., diazomethane, diazofluorcnc. ethyl diazoacetate. and phenyldiazoniethane ). However, depending on the reaction conditions, carbenes arc not always the reactive species. Cyclopropanes are often obtained by decomposition of pyrazolines which arise from 1,3-dipolar cycloaddilion reactions (see Section 2.1.1.6.2.3.1.). Even when reactions are performed under irradiation, pyrazolines can be obtained as the result of a diradical addition. ... 

Finally, a racemic cyclopropanation process has also been developed that utilizes an iron Lewis acid catalyst (72) that presumably proceeds through an iron carbene intermediate (73) (Scheme 28). The catalyst is activated by reaction with diazo compounds to produce an intermediate (74) that loses dinitrogen see Dinitrogen Dinitrogen Complexes) to afford the cyclopropane. This chemistry has been extended to the production of epoxides and aziridines and has recently been reviewed. ... 

Although reaction of a,/3-unsaturated carbonyl compounds with diazo compounds generally gives cyclopropyl compounds in low yields, in the presence of SbFs, the cyclopropanation of a,)8-unsaturated carbonyl compounds with diazocarbonyl compounds proceeds very well to produce the desired products in good yields (Eq. 22) [41]. 

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