Cyclopropanations vinylcarbenoids

Section 14.2 describes the highly stereoselective cyclopropanation chemistry of the donor/acceptor-carbenoids (Fig. 14.1a) [16]. This section introduces the range of vinyl, aryl, alkynyl, and heteroaryl functionalities that have been used as donor groups in this chemistry. Also, chiral auxiliaries and chiral catalysts that achieve high asymmetric induction in this chemistry are described [25]. The next two sections cover chemistry that is unique to the vinylcarbenoid system, namely [3-t4] cycloaddition with dienes (Fig. 14.1b see also Section 14.3) [13] and [3-1-2] cycloaddition with vinyl... 

The vinylcarbenoid [3-1-4] cycloaddition was applicable to the short stereoselective synthesis of ( )-tremulenolide A 73 and ( )-tremulenediol A 74 (Scheme 14.7) [81]. The key step is the cyclopropanation between the cyclic vinyldiazoacetate 69 and the functionalized diene 70, which occurs selectively at the ds-double bond in 70. Because of the crowded transition state for the Cope rearrangement of the divinylcyclopropane 71, forcing conditions are required to form the fused cycloheptadiene 72. The stereo-... 

The reaction of vinylcarbenoids with vinyl ethers can lead to other types of [3 + 2] cycloadditions. The symmetric synthesis of 2,3-dihydrofurans is readily achieved by reaction of rhodium-stabilized vinylcarbenoids with vinyl ethers (Scheme 14.17) [107]. In this case, (J )-pantolactone is used as a chiral auxihary. The initial cyclopropanation proceeds with high asymmetric induction upon deprotection of the silyl enol ether 146, ring expansion occurs to furnish the dihydrofuran 147, with no significant epi-merization during the ring-expansion process. 

The reaction of vinylcarbenoids with allylic C-H bonds leads to a remarkable transformation, a combined C-H insertion/Cope rearrangement, which is reminiscent of the tandem cyclopropanation/Cope rearrangement of vinylcarbenoids. An interesting application of this chemistry is the asymmetric synthesis of the antidepressant (-i-)-ser-traline 191 (Scheme 14.26) [134]. The Rh2(S-DOSP)4-catalyzed reaction of the vinyldia-zoacetate 189 with 1,3-cyclohexadiene generates the 1,4-cyclohexadiene 190 in 99% enantiomeric excess. The further conversion of 190 to (-t)-sertraline 191 is then achieved using conventional synthetic transformations. 

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... 

Recently, cyclopropane derivatives were produced by a ruthenium-catalyzed cyclopropanation of alkenes using propargylic carboxylates as precursors of vinylcarbenoids [51] (Eq. 38). The key intermediate of this reaction is a vinylcarbene complex generated by nucleophilic attack of the carboxylate to an internal carbon of alkyne activated by the ruthenium complex. Then, a [2+1] cycloaddition between alkenes and carbenoid species affords vinylcyclo-propanes. 

The rhodium(ii)-catalyzed intramolecular reaction between linked vinyldiazomethanes and pyrroles leads to a novel synthesis of fused tropanes <1996JOC2305>. The reaction occurs by a stepwise [3- -4]-annulation mechanism between a rhodium-stabilized vinylcarbenoid intermediate and the pyrrole rather than by the typical tandem cyclopropanation/Cope rearrangement sequence. The outcome of the reaction is very sensitive to the vinylcarbenoid structure. In particular, the presence of a siloxy substituent on the vinylcarbenoid strongly favors the formation of fused tropanes 1063 or 1064 (Scheme 206) <1996JOC2305>. 

An alternative strategy for achieving asymmetric control may be by covalent attachment of a chiral auxiliary to the carbenoid. This strategy has so far met with rather limited success in cyclopropanation reactions (see eq. (3) for a similar palladium-catalyzed reaction). However, the use of a-hydroxy esters as chiral auxiliaries with stabilized rhodium(II) vinylcarbenoids allowed entry into both series of enantiomeric vinylcyclopropanes with predictable stereochemistry. Optical yields are fair to excellent [14] and the outcome of the reaction was rationalized on the basis of interactions between the carbonyl oxygen of the chiral auxiliary and the carbenoid carbon. The strategy led to an efficient synthesis of optically active hydroxy vitamin D3 ring A [28]. 

The tandem cyclopropanation/Cope rearrangement sequence between metal-stabilized vinylcarbenoids and dienes is more widely applicable, since this method allows cyclopropanes with a wide range of substitution patterns to be synthesized, and the carbenoids are readily prepared by heating a vinyldiazomethane in the presence of a metal salt829,... 

Reaction with benzene follows a similar pathway, yielding a bicyclo[3.2.2]nonatriene structure. Vinylcarbenoids also react with pyrroles to give tropanes via a cyclopropanation-Cope rearrangement route. The direct addition of carbenes to acetylenes does not give satisfactory yields of cyclopropanes, but the rhodium carboxylate catalysed reaction of diazo compounds with acetylenes is a useful source of cyclopro-panes. Carbenoids can also attack a carbonyl oxygen atom, giving rise to a zwitterion (249). An excellent review of intramolecular carbenoid reactions has appeared. ... 

Having developed highly effective asymmetric cyclopropanation protocols for vinylcarbenoids, the extension to the [344] annulation of dienes was evaluated. Rhodium(II) acetate catalyzed decomposi-... 

De Meijere and co-workers have reported on the reactions of the parent vinyldiazomethane and chlorinated vinyldiazomethanes with oxygenated dienes. Rhodium(II) acetate catalyzed decomposition of these vinyldiazomethanes in the presence of 2-siloxydienes proceeds in good overall yields (Scheme 15). Because the vinylcarbenoid does not contain the donor/acceptor combination of the carbenoids derived from vinyldiazoacetates, the stereoselectivity of the cyclopropanation is poor and mixtures of the [344] annulation products and the trans-divinylcyclopropanes are formed. 

The asymmetric induction in vinylcarbenoid cyclopropanations can also be rationalized according to these models. Structure 61 represents the model for the asymmetric induction with the (/ )-pan-tolactone auxiliary. Using the same trajectory for the alkene ap-... 

To avoid the formation of alkylated products, the reaction was repeated with iV-acylated pyrroles, such that the pyrrole ring would be less electron-rich and less prone to rearomatize. Rhodium(II) acetate catalyzed decomposition of the vinyldiazomethane 4 in the presence of A-carbomethoxy pyrrole results in the formation of the [3+4] annulation product (entry 1, Table 12), and this reaction is applicable to a range of vinylcarbenoid derivatives. The tropanes are formed as the endo isomers, which is the expected stereochemistry for the tandem cyclopropanation/Cope rearrangement sequence. 

The formation of isomeric mixtures of cyclopropanes is not an issue in intramolecular reactions between vinylcarbenoids and dienes because the Stereochemistry of cyclopropanation is controlled by diene geometry. In the case of 102 where the double bond nearest the ester tether is trans, cyclopropanation would generate cis-divinylcyclo-propanes which would readily rearrange to cycloheptadienes (Table 15). The intramolecular cyclopropanation of trom -dienes by vinylcarbenoids is feasible even though the intermolecular cyclopropanation of a tran -alkene does not occur. Several examples of this type of intramolecular reaction are shown in Table 15. ° In contrast, when the double bond nearest the tether is cis, as with 103, the tra j-divinylcy-clopropane 104 is formed in 94% yield (Scheme 37). ... 

Carbenoid Reactions. Other synthetically useful reactions include carbenoid addition to form 2-oxabicyclo[3.1.0]hex-3-ene systems. 1 The reaction of vinylcarbenoids with furan provides two products (eq 22). These results may be rationalized invoking a nons3tnchronous cyclopropanation mechanism that leads to two possible dipolar transition states. - ... 

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