Reduction methylenecyclopropanes

Ethenylcyclopropyl tosylates 131 and 2-cyclopropylideneethyl acetates 133, readily available from the cyclopropanone hemiacetals 130, undergo the re-gioselective Pd(0)-catalyzed nucleophilic substitution via the unsymmetrical 1,1-dimethylene-jr-allyl complexes. For example, reduction with sodium formate affords a useful route from 131 to the strained methylenecyclopropane derivatives 132. The regioselective attack of the hydride is caused by the sterically... 

Methyl 2-bromo-2-cyclopropylideneacetate (11a) has never been tested in these reactions, but has been used as a starting material for the stepwise construction of 1,6-heptadienes with methylenecyclopropane units for intramolecular Heck reactions. Thus, bromo ester 11a, after reduction, subsequent conversion of the resulting alcohol to the bromide and coupling with enolates of substituted malonates, was transformed into dienes of the type 254 (Scheme 73) - versatile synthetic blocks for the preparation of functionally substituted spirocyclopropanated bicyclo[4.3.0]nonenes 255a-d by a domino Heck-Diels-Alder reaction [122a]. 

In the hydrocarbonation of methylenecyclopropanes 8 with nitriles, the hydro-palladation of 8 with 16 gives the alkylpalladium complexes 23 and/or 24 (Scheme 5). The complex 23 would undergo rearrangement by distal bond cleavage to give the Jt-allylpalladium 25 (route A). The reductive elimination of Pd(0) from 25 produces 9. The palladium complex 24 would isomerize to the Jt-allylpalladium complex 27 via proximal bond cleaved ring-opened intermediate 26 (route B). The reductive elimination of Pd(0) from 27 gives 10. 

Nickel(0)-catalyzed [3 + 2] cycloadditions of methylenecyclopropanes with A(-substituted maleimides (56 equation 22) lead almost exclusively to 5-alkylidenehexahydro-l//-cyclopenta[c]pynolo-l,3-diones (57) and (58 equation 23). A similar reaction occurs in the presence of a palladium(O) catalyst, but with lower selectivity. Unsubstituted maleimide and maleic anhydride do not undergo this cycloaddition. Ozonolysis of (57) and (58) into the corresponding ketone derivatives (62-78% yield) followed by reduction of both carbonyl groups gives l//-cyclopenta[c]pynoles, which are of interest with regard to their pharmacological activity (98% yield). ... 

Indeed, both kinds of cycloaddition products (Type A and Type B) can be obtained in the presence of Ni(0) catalysts while Pd(0) catalysts exclusively lead to Type A codimers. The real course of these reactions however is somewhat more complicated. While distal ring-opening via Route a really leads to cycloaddition products of Type A, proximal ring-opening via Route b results only in an isomerization of methylenecyclopropane. Cycloaddition products of Type B are obtained indirectly via oxidative coupling of two alkene units with low-valent nickel followed by a cyclo-propylmethyl/3-butenyl rearrangement22,148b). Reductive elimination terminates the catalytic cycle (Eq. 78). 

A further support for the mechanism outlined in Eq. 118 is that with Ni(0) catalysts a second type of [3+2]-cycloaddition can occur which involves the oxidative coupling of two alkenes coordinated at the nickel (one must be methylenecyclopropane). The initially formed nickelacyclopentane derivative may collapse to give a spiro[2.3]cyclohexane derivate or rearrange into a 4-methylenenickelacyclohexane derivate, which at the end of this catalytic cycle gives methylenecyclopentanes with a new substitution pattern by reductive elimination (see Eq. 78 and Scheme 8). 

Generation of the radical by reduction of a 1-bromomethylcyclopropene 10 is less selective, and the methylenecyclopropane 11 is obtained in only moderate yield, together with a number of ring-opened products. ... 

The simplest system that can react according to this scheme is a cyclobutanol a-substituted with a leaving group. 2-Bromocyclobutanol, prepared by lithium aluminum hydride reduction of 2-bromocyclobutanone (obtained by bromination of cyclobutanone, readily available from methylenecyclopropane ), and 2-tosyloxycyclobutanol, also prepared by lithium aluminum hydride reduction of 2-tosyloxycyclobutanone (available from 2-hydroxycyclobutanone ), undergo quantitative ring contraction to cyclopropanecarbaldehyde (1), on simple treatment with aqueous sodium hydroxide. 

When a similar palladium(0)-catalyzed reaction is performed in an acidic medium at room temperature, i.e. in the presence of acetic acid, different products are formed. These result from a reductive ring cleavage of the methylenecyclopropane (see Section 2.2.2.1. for details) and subsequent intramolecular Diels — Alder reaction with the unsaturated side chain in the case of 5-methylenehept-6-enyl propenoate (5) to ultimately yield 3-oxabicyclo[6.3.1]dodec-8-en-2-one (7). ( )-Octa-5,7-dienyl propenoate (6), however, is stable under the reaction conditions. Product 4, obtained from the acid-free reaction, has thus been proven to be different from the potential products of an isomerization/Diels —Alder addition sequence. 

In earlier investigations, asymmetric nickel-catalyzed isomerization and cyclodimerization of methylenecyclopropane was found to give l-methylene-2-vinylcyclopentane44. The nickel catalyst system was prepared by reduction of NiBr2L2 with butyllilhium. With tributylphosphane as ligand a 91% yield of the dimerization product was obtained. With dibromobis(( - )-methyl(phenyl)propylphosphane]nickel and butyllithium, optically active (no enantiomeric excesses given) l-methylene-2-vinylcyclopentane of unknown absolute configuration was obtained in 30% yield. Involvement of a n-allyl intermediate is proposed (loc. cit. 141 in ref 45). 

Finally, the influence of chiral phosphanes in the phosphane-modified nickel(0)-mediated codimerization process has been investigated with reasonable success63. The enantioselectivity of the addition of methylenecyclopropane to methyl acrylate in toluene has been shown to be dependent on the phosphane employed. Reduction of the ester functionality to the corresponding alcohol enables determination of the enantiomeric excess75. 

The concept of ring opening of cyclopropylcarbinyl radicals has been extended to substituted methylenecyclopropanes. As shown in Scheme 4, the crucial step in the reaction sequence is the regioselective addition of a substituted thiyl radical. After opening of the cyclopropane ring, the resulting radical adds to the olefin. Subsequent cyclization and reductive regeneration of the thiyl radical with concomitant liberation of the methylenecyclopentane product complete this transformation [6]. 

The involvement of metallacycles has been proposed for the [3+2] cycloaddition of meth-ylenecyclopropanes with alkenes to produce methylenecyclopentanes.l Oxidative cyclization of a methylenecyclopropane and an electron-deficient alkene produces a spi-rocyclic metallacyclopentane 86. Cyclopropane ring opening followed by reductive elimination affords the observed methylenecyclopentane products 87 and 88 (Scheme 65). Another report describes the novel use of nanostructured nickel clusters as catalysts. ]... 

Like other pyrazolines, 4-methylene-1-pyrazoline (MP) undergoes thermal extrusion of dinitrogen to form methylenecyclopropane (MCP) [35], but it does so much more rapidly the energy of activation is about 9 kcal/mol lower than that of the parent 1-pyrazoline, more than enough to offset a hundredfold reduction in the pre-exponential factor [40, 41]. This kinetic behaviour is prima facie evidence that the reaction proceeds stepwise via a triplet intermediate. The obvious choice was trimethylenemethane (TMM), that had been shown to have a triplet ground-state [36, 37, 38], in confirmation of numerous theoretical predictions [39], [18, pp. 141ff.j. 

Reactions of arenes carrying a coordinating substituent with alkenes may give alkylated derivatives when catalysed by ruthenium biscarboxylate complexes. Experiments with deuterium-labelled compounds indicate that carbon-hydrogen metallation is reversible, so that reductive elimination from intermediates such as (90) is rate determining. Carboxylate-assisted ruthenium catalysis also allows the reaction of 2-arylpyridines with methylenecyclopropane to give derivatives, (91), in which the cyclopropane ring is conserved. ... 

The hydrosilylation of methylenecyclopropanes is proposed to proceed via oxidative addition to the olefin, followed by rhodium migration across the strained cyclopropane ring, and eventual reductive elimination to give the silyl-substituted olefins. The process is compatible with aromatic and aliphatic substitution on the olefin and often requires heating. Additionally, cyclopropyl-substituted methylenecyclopropanes may be selectively silylated to give alkenes containing one, two, or three /3-silylated olefin chains. 

Diboration of Unsaturated Hydrocarbons. B2pin2 adds to unsaturated hydrocarbons in the presence of a catalytic amount of a Pt complex to afford diborated products in high yield with excellent regio- and stereoselectivity. The reaction is recognized to proceed through a catalytic cycle, which involves (a) oxidative addition of the B-B bond to Pt , (b) insertion of the unsaturated hydrocarbon into the B-Pt bond, and (c) reductive elimination of the product to regenerate Pt (eq 1). The diboration of alkynes, allenes, conjugated dienes, methylenecyclopropanes, anda, -unsaturated carbonyl compounds is efficiently catal) ed by phosphine-based Pt complexes (eqs 2-6), whereas phosphine-free Pt complexes are favorable for the reaction of simple alkenes because of the low coordination ability of the alkene over phos-... 

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