Stoichiometric cyclopropanations

Because electrophilic carbene complexes can cyclopropanate alkenes under mild reaction conditions (Table 3.1) [438,618-620], these complexes can serve as stoichiometric reagents for the cyclopropanation of organic compounds. Thoroughly investigated carbene complexes for this purpose are neutral complexes of the type (C0)5M=CR2 (M Cr, Mo, W) and cationic iron(IV) carbene complexes. The mechanism of cyclopropanation by electrophilic carbene complexes has been discussed in Section 1.3. 

Experimental Procedure 3.2.1. Cyclopropanation with an Iron Carbene Conqjlex 1,1-Diphenylcyclopropane [468] 

Cyclopropanations with carbene complexes, such as those listed in Tables 3.1 and 3.2, are usually stereospecific (i.e. Z-alkenes yield cA-cyclopropanes) [29]. This suggests, in agreement with theoretical investigations [28], that this reaction is a concerted process. One remarkable feature of these cyclopropanation reactions is the high cii -diastereoselectivity frequently observed [619,629]. 

Enantioselective cyclopropanations using enantiomerically pure tungsten [54], iron [458,483,630], and ruthenium [581] carbene complexes have also been at- 

Experimental Procedure 3.2.2. Cyclopropanation with a Titanium Carbene Complex (E)-l-Hexyl-2-(2-phenylethenyl)cyclopropane [33] 

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The molybdenum complex 1, a typical high-valent Schrock-type carbene, efficiently catalyzes the self-metathesis of styrene. On the other hand, the cationic iron complex 3 does not induce metathesis but stoichiometrically cyclopropanates styrene. The tungsten complex 2, again a Fischer-type carbene complex, mediates... 

Fig. 3.32. Catalytic and stoichiometric cyclopropanation of alkenes with carbene complexes.

Cyclopropanations with diazomethane can proceed with surprisingly high diastereo-selectivities (Table 3.4) [643,662-664]. However, enantioselective cyclopropanations with diazomethane and enantiomerically pure, catalytically active transition metal complexes have so far furnished only low enantiomeric excesses [650,665] or racemic products [666]. These disappointing results are consistent with the results obtained in stoichiometric cyclopropanations with enantiomerically pure Cp(CO)(Ph3P)Fe=CH2 X , which also does not lead to high asymmetric induction (see Section 3.2.2.1). 

Numerous highly enantioselective ring-forming reactions have also been discovered with the assistance of 1. Cyclopropanation with the rhodium complex of 1 furnishes rranr-cyclopropanes selectively (eq l)y A discrete ruthenium vinyl carbene was similarly successful in the stoichiometric cyclopropanation, whereas enantioselection in the copper(I)-catalyzed variant was nonselec-... 

The chiral ruthenium(II) carbene complex 8, prepared from diazo(trimethylsilyl)methane, (p-cymene)2ruthenium(II) chloride, and 2,6-bis(4-isopropyloxazolinyl)pyridine, has been introduced as catalyst for the enantioselective cyclopropanation of alkenes with ethyl diazoacetate. The carbene complex 8 also serves as a transfer reagent for trimethylsilylcarbene and cyclopro-panates styrene in 34% yield. This reaction demonstrates the similarities between catalytic and stoichiometric cyclopropanations and between in situ generated and isolated transition metal carbenes. 

Allylic acetates react with ketene silyl acetals. In this reaction, in addition to the allylated ester 468, the cyclopropane derivative 469. which is formed by the use of bidentate ligands, is obtained[303]. Formation of a cyclopropane derivative 471 has been observed by the stoichiometric reaction of the 7r-allylpal-... 

Larock has developed a new catalyst system for the Pd-catalyzed cyclization of olefinic tosylamides. Whereas typical conditions require either stoichiometric amounts of Pd(II) salts or catalytic amounts of Pd(II) in the presence of benzoquinone as a reoxidant, the new catalyst system utilizes catalytic Pd(OAc)2 under an atmosphere of O2 in DMSO with no additional reoxidant <96JOC3584>. Although o-vinylic tosylamides 76 can be cyclized to Af-tosylindoles 77 using this catalyst system, PdCla/benzoquinone is more effective for such cyclizations. Interestingly, in the case of o-allylic tosylanilides, the cyclization can be modulated to afford either dihydroindole or dihydroquinoline products. In a related approach involving a common 7i-aUyl Pd-intermediate, 2-iodoanilines were coupled with vinylic cyclopropanes or cyclobutanes in the presence of a Pd catalyst to afford dihydroindoles <96T2743>. 

Ruthenium porphyrin complexes are also active in cyclopropanation reactions, with both stoichiometric and catalytic carbene transfer reactions observed for Ru(TPP)(=C(C02Et)2> with styrene. Ru(Por)(CO)orRu(TMP)(=0)2 catalyzed the cyclopropanation of styrene with ethyidiazoacetate, with aiiti.syn ratios of 13 1... 

The use of stoichiometric ruthenium-NHC complexes generated in situ from [Ruljd-COCKp-cymene)], an imidazohnm salt [4] or an imidizol(idin)ium-2-carboxylate [4] has been applied in the cyclopropanation of styrene 5 with ethyl diazoacetate (EDA) 6 (Scheme 5.2). No base was necessary when imidazolium-2 carboxylate were employed. The diastereoselectivity was low and the cis/trans ratio was around 50/50 (Table 5.1). Although the diastereoselectivity was moderate, the reaction was highly chemoselectivity as possible side reactions (homologation, dimerisation and metathesis) were totally or partially suppressed. 

It has been demonstrated that in these cases cyclopropane formation is reversible and thermodynamically favorable [124]. Recently, a single example of the stoichiometric version of this reaction has been independently reported by Fernandez-Mateos [116]. 

The q1-coordinated carbene complexes 421 (R = Ph)411 and 422412) are rather stable thermally. As metal-free product of thermal decomposition [421 (R = Ph) 110 °C, 422 PPh3, 105 °C], one finds the formal carbene dimer, tetraphenylethylene, in both cases. Carbene transfer from 422 onto 1,1-diphenylethylene does not occur, however. Among all isolated carbene complexes, 422 may be considered the only connecting link between stoichiometric diazoalkane reactions and catalytic decomposition [except for the somewhat different results with rhodium(III) porphyrins, see above] 422 is obtained from diazodiphenylmethane and [Rh(CO)2Cl]2, which is also known to be an efficient catalyst for cyclopropanation and S-ylide formation with diazoesters 66). 

Cyclopropanes in low yield were first noted in 1964 by Banks and Bailey (12) during the disproportionation of ethylene, but little significance was attached to that observation until recently, because such products had no obvious relevance to early mechanistic concepts based on pairwise rearrangements of bisolefin complexes. However, the subsequent adoption of carbenelike species as metathesis intermediates (4) provided a foundation for later development of cyclopropanation concepts. The notable results of Casey and Burkhardt (5) made an impact which seemed rather neatly to unify mechanistically the interconversion of cyclopropanes and metathesis olefins, although the reactions which they observed were stoichiometric rather than catalytic [see Eq. (4)]. Nevertheless, their work indicated a net redistribution of =CPh2 and =CH2 from (CO)5W=CPh2 and isobutylene, respectively, to form CH2=CPh2. Dissociation and transfer of CO yielded W(CO)6. Unfortunately, the fate of the isopropylidene moiety remained unknown. In 1976,... 

The course of decomposition of confirmed or presumed metallocyclo-butane intermediates is important, but most results reported deal with stoichiometric rather than catalytic processes. Retention of the 3-carbon skeleton via pathways d or f in Eq. (26) occurs much more frequently than does cleavage to metathesis-related products. For example, thermolysis of phenyl-substituted platinocyclobutanes yields propenylben-zenes and phenyl-cyclopropane, but no styrene or ethylene (77). Similarly, the decomposition of tantalum carbene adducts (8) with olefins... 

Ukaji et al.117 reported an enantioselective cyclopropanation reaction in which moderate enantiomeric excess was obtained when a stoichiometric amount of diethyl tartrate was used as a chiral modifier. Takahashi et al.118 achieved better results using the C2-symmetric chiral disulfonamide 205 as the chiral ligand. 

HCCl2C00Me could be used instead of CHCI3 with similar results [128]. For (43a), cyclization by intramolecular Sn2 reaction competes with protonation, and when stoichiometric amounts of EGB and CHCI3 were used, the cyclopropane derivative was the main product. Scheme 32, since protonation of the intermediate anion now has to be from (33H), which is less acidic than CHCI3 [128],... 

Table 2.16. Cyclopropanations with stoichiometric amounts of heteroatom-substituted carbene complexes.

In addition to catalytically active transition metal complexes, several stable, electrophilic carbene complexes have been prepared, which can be used to cyclopropanate alkenes (Figure 3.32). These complexes have to be used in stoichiometric quantities to achieve complete conversion of the substrate. Not surprisingly, this type of carbene complex has not attained such broad acceptance by organic chemists as have catalytic cyclopropanations. However, for certain applications the use of stoichiometric amounts of a transition metal carbene complex offers practical advantages such as mild reaction conditions or safer handling. 

Fig. 3.33. Stoichiometric, intramolecular cyclopropanations with iron(IV) carbene complexes [477,624],...

Table 3.1. Cyclopropanation with stoichiometric amounts of chromium, molybdenum and tungsten carbene complexes.

Acceptor-substituted carbene complexes are highly reactive intermediates, capable of transforming organic compounds in many different ways. Typical reactions include insertion into o-bonds, cyclopropanation, and ylide formation. Generally, acceptor-substituted carbene complexes are not isolated and used in stoichiometric amounts, but generated in situ from a carbene precursor and transition metal derivative. Usually only catalytic quantities of a transition metal complex are required for complete conversion of a carbene precursor via an intermediate carbene complex into the final product. 

More recent reports from Cordova [155] and Wang [156] have described the cyclopropanation of a, P-unsaturated aldehydes 99 with diethyl bromomalonates 100 and 2-bromo ethyl acetoacetate catalysed by a series of diaryIprolinol derivatives. Both describe 30 as being the most efficient catalyst in many cases and optimal reaction conditions are similar. Some representative examples of this cyclopropanation are shown in Scheme 40. The transformation results in the formation of two new C-C bonds, a new quaternary carbon centre and a densely functionalised product ripe for further synthetic manipulation. Triethylamine or 2,6-lutidine are required as a stoichiometric additive in order to remove the HBr produced during the reaction sequence. The use of sodium acetate (4.0 equivalents) as an additive led to subsequent stereoselective ring opening of the cyclopropane to give a,P-unsaturated aldehydes 101. It can be envisioned that these highly functionalised materials may prove useful substrates in a variety of imin-ium ion or metal catalysed transformations. 

Mixed ( )-cinnamyl acetals 460 undergo the enantioselective carbolithiation readily in the presence of stoichiometric or catalytic amounts, as low as 1 mol%, of (—)-sparteine (11) (equation 126) °. When quenching the reaction mixture of 461, 462 below —50°C with MeOH/HCl, the alcohols 463 are obtained with good yields and excellent ee values. However, upon warming to 20 °C, a 1,3-cycloelimination from conformation 462 gives rise to the formation of optically active trani-cyclopropanes 464 °. 

E. Stereoselective Cyclopropanation of Alkenes using Stoichiometric Chiral... 

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