Magnus cyclization

For example, as shown by calicheamicin, cyclic enediynes have a lower activation barrier than acyclic enediynes. As suggested by Nicolaou in 1988, the distance between the acetylenic carbons that form the covalent bond influences the rate of cyclization. Another theory developed by Magnus and Snyder is based on the molecular strain between ground state and transition slate this seems to be more general, especially for strained cyclic systems. Often, as both the distance and the strain are not known, the development of suitable precursors remains difficult, as exemplified by the following enediyne, in which a slight change leads to a cycloaromatization ... 

Gange, D. Magnus, P. An unusual new allene cyclization reaction. Synthesis of dihydro-furan-3(2H)-ones. J. Am. Chem. Soc. 1978, 100, 7746-7747. 

A significant advance in the use of Friedel-Crafts acylation of alkenes to prepare divinyl ketones was the employment of vinylsilanes to control the site of electrophilic substitution. Two groups have developed this approach to cyclopentenone annulation using slightly different strategies. In the method described by Magnus the reagent vinyltrimethylsilane (80) is used primarily as an ethylene equivalent (equation 44). The construction of bicyclic systems followed readily as Nazarov cyclization proceeded under the reaction conditions. Tin(lV) chloride was found to be the most effective promoter of the overall transformation. As expected the position of the double bond is thermodynamically controlled. 

Szdntay s later synthesis (343) of 3-oxovincadifformine consisted essentially of an independent synthesis (Scheme 75) of Kuehne s tetracyclic aminoester 562a, which on debenzylation cyclized to 3-oxovincadifformine (97). The double bond was then introduced at the 14,15-position via the thiolactam, in a procedure reminiscent of that adopted by Magnus in his synthesis of 3-oxotabersonine (107). Desulfurization of the intermediate unsaturated thiolactam 586 gave yet another synthesis of tabersonine, whereas oxidative removal of the si r atom gave 3-oxotabersonine (107). Alternatively, condensation of the starting tryptamine derivative 587 with... 

Magnus and coworkers have concluded that the cyclization rate of enediynes depends on the strain energy of the transition state leading to the diyl (Scheme 16) [38]. They examined bicyclic systems 107 and 108, comparing their rates of cyclization and discovered that despite similar cd distances, substrate 107 cyclizes much faster. By performing calculations on a model system 111, they concluded that the greater strain energy of product 109 retards the rate of cyclization relative to 110. This work was carried out under the assumption that the transition state is product-like. 

Magnus et al. obtained both enantiomers of 9 with considerable effort by acylation of 6 with (+)-(/ )-p-toluenesulfinylacetic acid and cyclization of the resulting sulfoxide 7b, separation of the four diastereomers formed this way, combination of the pairs with the same absolute configurations at C6 and C7, and subsequent conversion into the two enantiomers 9 and ent-9. [9a] The cyclization of sulfoxide 7b yields the two products enantiomeric at C6 and C7 in a 55 45 ratio. This is why this route is not only laborious but then only insignificantly more efficient than resolution. 

The next steps in the synthesis include the multistep conversion of E)-15 into 16, subsequent cleavage of the silyl ether protecting group, and cyclization of 17, which cannot be isolated, to provide hexacyclic 18. With the reductive removal of the sulfonamide Magnus et al. arrived at their first goal, the total synthesis of the Wieland-Gumlich aldehyde (2). The conclusion of the total synthesis of strychnine is also within reach the authors succeed in converting 2 into the natural prod-... 

An interesting cyclization reaction was reported that involved the reaction of dienes, diynes, or ene-ynes with transition metals to form cyclopentenone derivatives in the presence of carbon monoxide.363 in a simple example, ene-yne 444 was heated with dicobalt octacarbonyl and CO to give a 68% yield of 445.364 jjjj transformation has become an important synthetic tool known as the Pauson-Khand reaction.365 jhe mechanism probably involves insertion of the alkene (or alkyne) into the transition metal bond, which is why it is presented in this section. Formally, it is a [2+2+l]-cycloaddition, but the accepted mechanism is the one proposed by Magnus,364 and shown in Figure 13.8.366 n has been stated that further study is required to... 

A Meerwein arylation protocol was employed by Rancher and Koolpe to construct the requisite o-nitro carbonyls for indolization. Thus, arylation of o-nitrophenyldiazonium chlorides with vinyl acetate or vinyl bromide followed by reductive cyclization of the adducts affords indoles (Scheme 4, equation 1) [19]. The Rancher indole synthesis has been adopted by Magnus on a multigram scale to... 

In 1985 both Magnus and Schore independently proposed identical mechanisms based on stereochemical and regiochemical preferences observed in the product. Magnus s hypothesis was based on the stereochemical results for an intramolecular cyclization. He proposed that the product arose from formation of a metallocycle intermediate 7 or 8, carbon monoxide insertion to give 9, acyl migration fi om cobalt to carbon and reductive elimination of cobalt to form 10. The relative thermodynamic stability of the metallocycles 7 and 8 controlled the final product ratio. In the... 

Scheme 10.60. An example of the Nazarov cycUzation effected on cyclopentenoyl chloride. The example shows a potential rationalization for the observation that treatment of the acid chloride with silver tetrafluoroborate in dichloromethane at -50°C followed by addition of l-(trimethylsilyl)-l-(phenylthio)ethene results in the formation of 4-(thiophenyl)bicyclo[3.3.0] oct-3-ene-2-one. It is argued that the cycUzation step is a concerted process (see Habermas, K. L. Denmark, S. E. Jones, T. K.The Nazarov cyclization, in Paquette, L. A. (ed.). Organic Reactions, Vol. 45, Wiley, Hoboken, NJ, 1994 Magnus, P. Quagliato, D. J. Org. Chem., 1985, 50,1621).

Structural subclass. The biogenesis of this compound was not studied the incorporation of dopamine instead of tyrosine at the early step of the biogenesis was hypothesized (Section 9.2). In addition, one can speculate for an intramolecular cyclization of the C8 hydroxy group of epibubbiaUne (43) to position C5. This hypothesis was discussed by Magnus (vide infra, Section 8.4). 

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