Stereospecific cyclization

When the chain bearing the allylsilane is one carbon longer, i.e., by the use of pentenylsilanes, cycloheptane rings can be formed. Both the (Z)- and (A )-isoiner of the (3-pentenyl)silanes can be synthesized selectively, but only the (Z)-(3-pentenyl)silane cyclized stereospecifically (complete 1,4-asymmetric induction). Both cthylaluminum dichloride and boron trifluoride diethyl ether complex promote the seven-membered ring formation35 43-48. 

Phenylprop-2-enyl sulfates are cyclized stereospecifically and with Markovnikov regiochemical control. These are endo-6 cyclizations. 

Keywords bisallene, cyclization, stereospecific, thermolysis, bismethylene-cy-clobutene... 

In a study of the mechanism and stereochemistry of the enamide photo-cyclization, Lenz has demonstrated that ethylidene and benzylidene isoquinoline enamides cyclize stereospecifically from the Z-isomer to yield 13-substituted oxoberberines in which the 13-substituent is quasi-axial and the C-13 and C-14 hydrogens are in a cis relationship. ... 

Z allylsilane (5ft) cyclized stereospecifically (Eq. 18). These results culminated in stereospecific syntheses of epi-widdrol (40) (Eq. 19) and a formal synthesis of widdrol. 

The stereospecific synthesis of an A ring synthon of la-hydroxy vitamin D has been carried out. The ( )-allcene is cyclized to give the (E -c.xo-diene 155, and the (Z)-allcene affords the (Z)-e,xo-diene 156 stereospecifically[125,126]. These results can be understood by the cis addition and syn elimination mechanism. 

Potassium Amides. The strong, extremely soluble, stable, and nonnucleophilic potassium amide base (42), potassium hexamethyldisilazane [40949-94-8] (KHMDS), KN [Si(CH2]2, pX = 28, has been developed and commercialized. KHMDS, ideal for regio/stereospecific deprotonation and enolization reactions for less acidic compounds, is available in both THF and toluene solutions. It has demonstrated benefits for reactions involving kinetic enolates (43), alkylation and acylation (44), Wittig reaction (45), epoxidation (46), Ireland-Claison rearrangement (47,48), isomerization (49,50), Darzen reaction (51), Dieckmann condensation (52), cyclization (53), chain and ring expansion (54,55), and elimination (56). 

Synthesis of 2-thioxopenams (76) has also been realized usiag a [sulfur, C-5] ring closure (117). Cyclization of 4-(3)-chloroazetidinone [88816-44-8] (77, R = R = SCOCH ), C22H22ClN20gS2, usiag imidazole ia aqueous dioxane proceeded stereospecifically to give the 5-(R)-thioxopenam [83362-57-6]... 

The converse situation in which ring closure is initiated by the attack of a carbon-based radical on the heteroatom has been employed only infrequently (Scheme 18c) (66JA4096). The example in Scheme 18d begins with an intramolecular carbene attack on sulfur followed by rearrangement (75BCJ1490). The formation of pyrrolidines by intramolecular attack of an amino radical on a carbon-carbon double bond is exemplified in Scheme 19. In the third example, where cyclization is catalyzed by a metal ion (Ti, Cu, Fe, Co " ), the stereospecificity of the reaction depends upon the choice of metal ion. 

Electrocyclic reactions of 1,3,5-trienes lead to 1,3-cyclohexadienes. These ring closures also exhibit a high degree of stereospecificity. The ring closure is normally the favored reaction in this case, because the cyclic compound, which has six a bonds and two IT bonds, is thermodynamically more stable than the triene, which has five a and three ir bonds. The stereospecificity is illustrated with octatrienes 3 and 4. ,Z, -2,4,6-Octatriene (3) cyclizes only to cw-5,6-dimethyl-l,3-cyclohexadiene, whereas the , Z,Z-2,4,6-octa-triene (4) leads exclusively to the trans cyclohexadiene isomer. A point of particular importance regarding the stereochemistry of this reaction is that the groups at the termini of the triene system rotate in the opposite sense during the cyclization process. This mode... 

The mercuration-demercuration sequence was applied to the stereospecific synthesis of 2 deoxy-o-hexopyranoside derivative via a mercury(ll) trifluoroace-tate-promoted cyclization [54] (equation 25)... 

The first objective was the conversion of L-tryptophan into a derivative that could be converted to pyrroloindoline 3, possessing a cis ring fusion and a syn relationship of the carboxyl and hydroxyl groups. This was achieved by the conversions shown in Scheme 1. A critical step was e. Of many variants tried, the use of the trityl group on the NH2 of tryptophan and the t-butyl group on the carboxyl resulted in stereospecific oxidative cyclization to afford 3 of the desired cis-syn stereochemistry in good yield. 

Model studies directed toward the synthesis of Ecteinascidin 743 employed an elegant Pictet-Spengler cyclization of phenethylamine 54 and the 1,2-dicarbonyl compound 55 to assemble the spiro tetrahydroisoquinoline 56 in a stereospecific fashion. " The silica-catalyzed condensation reaction provided 56 in excellent yield. 

A second direct route to an extended 3,4-dihydro-j8-carbolinium system (120) using the Bischler-Napieralski ring closure is based on the cyclization of intermediates of general structure 118. Three approaches to intermediates of this type have been developed in connection with stereospecific syntheses in the indole alkaloid field. The first approach, introduced independently by Stork and Hill and by van Tamelen and co-workers and often used... 

In addition there are certain other methods for the preparation such compounds. Upon heating of the thionocarbonate 2 with a trivalent phosphorus compound e.g. trimethyl phosphite, a -elimination reaction takes place to yield the olefin 3. A nucleophilic addition of the phosphorus to sulfur leads to the zwitterionic species 6, which is likely to react to the phosphorus ylide 7 via cyclization and subsequent desulfurization. An alternative pathway for the formation of 7 via a 2-carbena-l,3-dioxolane 8 has been formulated. From the ylide 7 the olefin 3 is formed stereospecifically by a concerted 1,3-dipolar cycloreversion (see 1,3-dipolar cycloaddition), together with the unstable phosphorus compound 9, which decomposes into carbon dioxide and R3P. The latter is finally obtained as R3PS ... 

The biomimetic approach to total synthesis draws inspiration from the enzyme-catalyzed conversion of squalene oxide (2) to lanosterol (3) (through polyolefinic cyclization and subsequent rearrangement), a biosynthetic precursor of cholesterol, and the related conversion of squalene oxide (2) to the plant triterpenoid dammaradienol (4) (see Scheme la).3 The dramatic productivity of these enzyme-mediated transformations is obvious in one impressive step, squalene oxide (2), a molecule harboring only a single asymmetric carbon atom, is converted into a stereochemically complex polycyclic framework in a manner that is stereospecific. In both cases, four carbocyclic rings are created at the expense of a single oxirane ring. 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

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