Cyclopropanation. alternative additives

Treatment of geminal dihalocyclopropyl compounds with a strong base such as butyl lithium has been for several years the most versatile method for cumulenes. The dihalo compounds are easily obtained by addition of dihalocarbenes to double--bond systems If the dihalocyclopropanes are reacted at low temperatures with alkyllithium, a cyclopropane carbenoid is formed, which in general decomposes above -40 to -50°C to afford the cumulene. Although at present a number of alternative methods are available , the above-mentioned synthesis is the only suitable one for cyclic cumulenes [e.g. 1,2-cyclononadiene and 1,2,3-cyclodecatriene] and substituted non-cyclic cumulenes [e.g. (CH3)2C=C=C=C(CH3)2]. 

The reported proposed sequence also offers two additional alternative mechanisms for the cyclodimerization of BCP (3), involving either intermediate 463 or 464 [6a, 13b]. However, they appear less likely, requiring successive three-membered ring fissions and formations. Alternatively, a thermally allowed concerted [jt2s + rt2a -I- pericyclic reaction involving the Walsh type molecular orbital of cyclopropane [124] has been proposed (Fig. 4) [13b]. 

However, the generation of cyclopropane derivatives was also shown to implicate an alternate route not requiring a metallocyclobutane transition state (14). In addition, a metathesis catalyst successfully converted certain cyclopropanes to metathesis-related olefins by way of a carbene elimination process (15-17), according to Eq. (3). 

Charette and Brochu have reported an alternate protocol for the Lewis acid-catalyzed cyclopropanation reaction of allylic alcohols, in which the uncatalyzed process is suppressed . The addition of Zn(CH2l)2 (1 equivalent) to an allylic alcohol (1 equivalent)... 

When pyrroles, triazoles and other nitrogen containing heterocyclic compounds react with dichlorocarbene, no addition to their carbon-carbon double bonds has been observed. In some cases the formation of cyclopropane adducts has been suspected however, alternate ways to explain the reaction products cannot be excluded [228]. 

The schematic representation of Figure 5 illustrates the paths relating one EE intermediate with four cyclopropane structures. An alternative schematic, Figure 6, shows the paths relating one cyclopropane with four EE intermediates by way of six transition structures. In addition to the paths given explicitly in Figures 5 and 6, there are 4 direct paths by way of EF transition structures relating each cyclopropane with one-center epimeriza-tion products. 

The formation of cyclopropane derivatives by photolysis of diazoalkanes in the presence of alkenes is believed to occur by photolytic decomposition of the diazoalkane to yield the carbene, followed by addition of this carbene to the alkene. Cycloaddition of this type has been reported in furan, dihydrofuran, and thiophene.198 Thus, photolysis of ethyl diazoacetate in thiophene yields the bicyclic sulfur heterocycle (215). Alternatively, photolysis of 3-diazo-l-methyl-oxindole (216) in cyclohexene leads to the formation of two isomers which are thought to have the spirocyclopropyl structure (217) photolysis in ethanol yields 3-ethoxy-1-methyloxindole.194... 

A net C—O to C—C bond chirality transfer has been demonstrated in the preparation of a cyclopropane (equation 344).428 Another C—O to C—C chirality transfer was accomplished starting with an optically active alkylidenetetrahydrofuran 429 Not only was complete stereospecificity via a double inversion mechanism observed, but, in addition, regioselectivity had to be exercised to avoid the alternate cycliza-tion to give a seven-membered ring product (equation 345). 

Dihalocydopropanes readily undergo reductive dehalogenation under a variety of conditions. Suitable choice of reagents and reaction conditions will allow the synthesis of monohalocyclopropanes or the parent cyclopropanes.19 " The ease of reduction follows the expected order I > Br > Cl > F. In general, complete reduction of dibromo and dichloro compounds is accomplished by alkali metal in alcohol,99-102 liquid ammonia103 or tetrahydrofuran (equations 28 and 29).104 The dihalocydopropanes can be reduced conveniently with LAH (equation 30).105 LAH reduction is particularly suited for difluoro compounds which are resistant to dissolving metal reductions.19 106 It is noteworthy that the sequence of dihalocar-bene addition to an alkene followed by the reduction of the dihalocyclopropyl compounds (equation 31) provides a convenient and powerful alternative to Simmons-Smith cyclopropanation, which is not always reliable. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

Given the rich variety of electron transfer induced reactions observed for cyclopropane systems, it is not surprising to find a similarly rich reactivity for systems comprised of two fused cyclopropane rings. For bicyclobutane systems, such as the trimethyl derivative (71), nucleophilic capture leads to addition with cleavage of the transannular bond (->72). Alternatively, the initial capture and ring opening may be accompanied by dehydrogenation (—>73) [246],... 

However, a respectable alternative to the direct [2 + l]-routes (a)-(c) is the variant using halo- or dihalocyclopropanes as precursors for the desired target molecules (path d). The cyclopropane ring is formed by addition of halocarbenes to the olefin and subsequent change of functionalities is achieved by treatment with nucleophiles. It is very unlikely that a direct substitution incorporates the donor-substituent. Instead an elimination/addition sequence with the intermediacy of a cyclopropene has to be assumed. 

Complexes (160) (see equation 35) undergo conversion to phenols upon thermolysis. Alternatively, treatment with AICI3 under a CO atmosphere gives an j)" -iron cyclohexadienone complex thermolysis or treatment with CuCl2 affords a phenol as well. Complexes (162), derived from nucleophihc addition to ( ) -pentadienyl)Fe(CO)3+ cations (see equation 37), can be converted to vinyl cyclopropanes by using CAN (equation 41). ... 

A homolytic cyclopropane C-C bond rupture that would furnish in turn a 1,3-diradical is also conceivable. However, it is always difficult to establish whether a purely diradical or ionic mechanism is in operation. Between these two extremes there exists a graded continuum of polarized diradicals of which the zwitterion represents the end of the spectrum. In addition, the continuous development of radical character during the formation of the transition state of a homolytic bond scission, called the continuous diradical, has been postulated to explain the behavior of some reactions. Alternatively, the contribution of a truly concerted transformation cannot be overlooked. ... 

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