Acceptor cyclopropanation

Therefore acceptor cyclopropanes 1 will be ring opened by nucleophiles N to provide products like 2 (homo Michael addition) as depicted in Eq. 1. On the other hand, electrophiles E+ cleave donor activated cyclopropanes 3 affording adducts 4 or 5 which demonstrates that the cyclopropane serves as a homoenolate equivalent in this sequence (Eq. 2). Seebach consequently classified these methods as umpolung with the cyclopropane trick 4. ... 

Addition of electrophilic carbenes to enamines usually does not proceed with good efficiency, very likely because of the disturbance by the Lewis basic nitrogen 15). If however the less basic enamide derivatives are used as olefins, high conversions to donor-acceptor cyclopropanes are possible. Thus cyclic carbamate 245, which itself originates from an oxycyclopropane, gives the bicyclic compound 246 almost quantitatively. Its cleavage with aqueous base provides lactone 247 that could be coupled with tryptophyl bromide to afford 248, a direct precursor of the alkaloid eburnamoni-ne 105>. 

The same disadvantage presents itself in the synthesis of bicyclic donor acceptor cyclopropanes (equation 89), which result in cyclopentenones after Barton fragmentation and aldol condensation... 

Bromination of Cyclopropanes. NBS gives bromination of donor-acceptor cyclopropanes by an electron-transfer (ET) mechanism (eq 30)7 ... 

Fused indole 232 resulted from the reaction of a donor-acceptor cyclopropane with an indole bearing a Michael acceptor at C2.The products were obtained in good yield with high diastereoselectivity (16 examples, 64-90% yield) (140L3954). Tetracyclic-fused indole 233 was prepared by a [3+3]-cycloaddition of an indol-2-yl carbinol with an azadiene (11 examples, 42-90% yield). This could be followed by an oxidative ring expansion promoted by (bis(trifluoroacetoxy)iodo)benzene to produce a series of indole azepinones (6 examples, 59-71% yield) (14CC11181). Fused indole 234 was synthesized by the first calcium(II)-promoted Nazarov cyclization (87% yield).The substituent a to the ester functionality could vary electron-rich arenes, heteroarenes, and secondary alkyl... 

As described earlier, quinone monoketals (e.g., 139) are not only good substrates for the DPM reaction, but they also participate in acid-catalyzed [5+2]cycloaddition reactions with styrene derivatives (e.g., p-methylstyrene) to givebicyclo[3.2.1]octenediones (e.g., 140) that can themselves participate in ODPM processes to give multiftinctional, donor-acceptor cyclopropanes (e.g., 141). The last type of conpound can participate in fiirther reactions generating several additional and novel scaffolds that may be useful in drug discovery settings. Meanwhile, iminium ethers that are readily derived from [5+2] cycloadducts of type 140 participate in ADPM rearrangements. 

DFT studies have been performed on two zinc carbenoid-mediated reactions. On (g) one hand, a mechanistic investigation of the one-carbon homologation of /3-keto-esters has revealed two competing pathways (i) formation of the donor - acceptor cyclopropane intermediate (41) and (ii) a reaction involving the cyclopropane transition state (42). A preference for the classical or the non-classical pathway is not clear... 

Photochemical oxa-di-jt-methane rearrangement of bicyclo[3.2.1]octa-noid scaffolds affords multifunctional, donor-acceptor cyclopropanes (34). Application of this reaction to bicyclo[2.2.2]octenones has been used as a key step in the total synthesis the hirsutane-type sesquiterpenes (-)-connatusin A (35), (+)-connatusin B (36), and the marine sesquiterpenoid 2-isocyanoallopupukeanane (37). ... 

Scheme 10.11 Ring-opening reaction of donor-acceptor cyclopropanes with amines.

The enantioselective 3 + 3-cycloaddition reaction of aromatic azomethine imines with donor-acceptor cyclopropane diesters produced 6,6,6-tricyclic dihydroquinolines in high yields (99%) and up to 98% ee. The side-arm-modified In-TOX/Ni(II) complex was shown to be an effective stereoselective catalyst for this reaction. The formal 3 + 3-cycloaddition reaction of allylic phosphonium ylides (127) to a, -unsaturated carbonyls (128) formed multi-substituted benzenes (129) in high yields (36-93%) (Scheme 38). °... 

Haubenreisser, S., Hensenne, R, Schroder, S., Niggemann, M. (2013). The alkynylmoiety as a donor for donor-acceptor cyclopropanes. Organic Letters, 15, 2262-2265. 

Ring opening of cyclopropane occurs under various conditions. In particular, cyclopropanes with unsaturated or electron-donating and -accepting substituents (donor-acceptor cyclopropanes) undergo facile ring opening hence, their reactions have been extensively studied [1]. However, reports on catalytic reactions of electron-neutral cyclopropanes are limited. 

VCPs with electron-withdrawing groups underwent facile ring opening under mild conditions. Palladium-catalyzed [3+2] annulation of donor—acceptor cyclopropanes with alkenes was first reported in 1985 [76]. Diastereo- and enantioselective [3+2] annulation was recently achieved by using the Trost ligand (Scheme 2.55) [77]. 

Transition-metal-catalyzed ring-opening functionalizations of donor - acceptor cyclopropanes have also been developed (Table 2.2). Addition of carbon nucleophiles to activated VCPs 69b and 69c in the presence of iron catalysts induced ring opening of the three-membered ring [81, 82]. A palladium pincer complex catalyzed ring-opening borylation of VCP 69c with 62(011)4 to produce... 

Scheme 2.58 Ni(0)-catalyzed rearrangement of l-acyl-2-vinylcyclopropane 73. Table 2.2 Ring-opening functionalizations of donor-acceptor cyclopropanes.

In contrast to the above reactions of donor-acceptor cyclopropanes involving electrophrhc n-allyl intermediates, umpolung of cyclopropanes was observed in iridium-catalyzed coupling of VCP and alcohols (Scheme 2.59) [87]. In the reaction, nucleophilic 3t-allyliridium species were used to achieve diastereo- and enan-tioselective carbonyl allylation. 

One significant limitations of both methods described above is that some types of donor-acceptor cyclopropanes such as the extensively studied 2-substituted cyclopropane-1,1-diesters are unable to produce the desired azides under then-conditions. In this regard, in 2015, Trushkov et al. developed a general and efficient method for ring-opening of various donor-acceptor cyclopropanes with NaN3 to synthesize a variety of polyfunctional azides (Scheme 6.27) [82]. The process proceeds with excellent regioselectivity and provides the products in moderate to... 

The (la)-promoted [3 + 2] cycloaddition of donor-acceptor cyclopropanes to nitriles is valuable for the synthesis of pyrroles (Scheme 9.49) [122]. The action of (la) on the cyclopropanes generates reactive 1,3-dipole equivalents, which adds to the C-N triple bond. 

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