Cyclization palladium mediated

Scheme 3.22 Potential mechanisms for the palladium-mediated cyclization...

Our studies of ( )-kinamycin F (6) motivated the development of a three-step sequence for synthesis of the diazofluorene function, comprising fluoride-mediated coupling, palladium-mediated cyclization, and diazo transfer. Our synthesis also features the strategic use of substrate bias to establish the trans- 1,2-diol of the target. 

A series of benzo[fc]benzo[2,3-cfjthiophen-6,9-diones 12 has been prepared in modest yields by palladium mediated cyclization of the precursors 13. However, the necessity to use stoichiometric amounts of the palladium source precludes cost effective preparation of the targets. The required substrates 13 may be constructed by palladium catalyzed reactions between the appropriate phenols with 2,3-dimethylbenzoquinone <06SC3319>. 

A copper-mediated cyclization of metallated thiophenes has been utilized to prepare polycyclic thiophenes and thiophene cyclophanes. Treatment of dibromide 106 in succession with M-butyllithium (halogen-metal exchange), zinc chloride (transmetallation), and copper chloride gave 7//-cyclopcnta[ 1,2-fc 4,3-6 dithiophene (107) <00H(52)761>. This conversion has also been achieved using a palladium-mediated cyclization performed in the presence of hexamethylditin . Copper-mediated cyclizations have also been applied to the syntheses of cyclopenta[2,l-6 3,4-A ]dithiophen-4-one (108) (three steps from 73) <00S1253> and cyclophane 109 <00CC2329>. 

Finally, fully reduced heterocycles have been prepared either from a sequential azomethine imine cycloaddition-palladium-mediated cyclization process <2003T4451>, or from the reaction of A-( l-benzotriazolylalkyU-AyV-disubstitutcd hydrazine with methyl vinyl ether <1997JOC8210>. 

As an alternative to this procedure, the amino group of 160 can be generated from the corresponding nitro derivative prepared from 158 and 159 by reduction with iron. Palladium-mediated cyclization of 160 produced the desired dibenzoxazepine 161 (Scheme 24) <2003JOC644>. Tandem reduction/reductive animation <2004JHC963> and reduction/lactamization <2006JHC1031> procedures were also described. 

The synthesis of highly substituted tetrahydrofurans by means of a multicomponent reaction based on this palladium-mediated cyclization process was reported by Balme and co-workers [94]. In this reaction, formation of enolate 103 by the initial 1,4-addition of an allylic alcohol to the conjugate acceptor 102 is followed by a... 

I.-F. Nguefack, V. Bolitt, and D. Sinou, Palladium-mediated cyclization on carbohydrate templates. 2. Synthesis of enantiopure tricyclic compounds, J. Org. Chem., 62 (1997) 6827-6832. 

A palladium-mediated cyclization which provides carbazole-1.4-quinones was improved by development of conditions which require substoichiometirc amounts of Pd(OAc),. /-Butyl hydroperoxide is used for reoxidation of Pd. <95TL1325> The same conditions, however, were only marginally successful (30% yield) for converting diphenylamine to carbazole. 

Boger reported studies on palladium-mediated cyclization to form the CDE ring system of lavendamycin, as shown in Eq. (2) [74-76]. These reactions were conducted with stoichiometric amounts of [Pd(PPh3)4] (2). When used in a 1 mol% quantity, 2 failed to catalyze these reactions, presumably because of the absence of a base. Until almost 10 years later, no palladium-catalyzed animation chemistry was reported, and few citations of the early amination chemistry existed. 

Stoichiometric palladium-mediated cyclization was used in natural product synthesis by Boger a number of years ago, as was noted in the introduction. More recently, an intramolecular palladium-catalyzed amination of a heteroaromatic halide has been used as a step in the synthesis of an a-carboline natural product analog [146]. As discussed above, the diphenylhydrazone arylation can also be used for nitrogen heterocycle synthesis [140]. 

Abstract This review gives an insight into the growing field of transition metal-catalyzed cascades. More particularly, we have focused on the construction of complex molecules from acyclic precursors. Several approaches have been devised. We have not covered palladium-mediated cyclizations, multiple Heck reactions, or ruthenium-catalyzed metathesis reactions because they are discussed in others chapters of this book. This manuscript is composed of two main parts. In the first part, we emphasize cascade sequences involving cycloaddition, cycloisomerization, or ene-type reactions. Most of these reaction sequences involve a transition metal-catalyzed step that is either followed by another reaction promoted by the same catalyst or by a purely thermal reaction. A simple change in the temperature of the reaction mixture is often the only technical requirement to go from one step to another. The second part covers the cascades relying on transition metalo carbenoid intermediates, which have recently undergone tremendous... 

Palladium-mediated cyclizations have lately become a central theme for the synthesis of many different types of heterocycles. It is not surprising, therefore, that... 

Another palladium-mediated cyclization enables 2-iodoaniline to be converted at 140 to quinoline by reaction with a substituted allyl alcohol in the presence of triphenylphosphine, HMPT and hydrogencarbonate. Allyl alcohol itself gives poor results in this reaction. 

Trost, B.M. and Chung, J.Y.L. (1985) Unusual substituent effect on a palladium-mediated cyclization a total synthesis of (+ (-sterepolide. Journal of the American Chemical Society, 107, 4586—4588. 

D.U. Palladium Mediated Cyclization Reactions. It is possible to use organopalladium chemistry for cyclization reactions. Treatment of 386 with the palladium catalyst ([dba]3Pd2, where dba = dibenzylidene acetone) led to cyclization that generated a five-membered ring (387) in 78% yield.227... 

The beauty of the tetracyclic cage design was that it left us with many choices of forming the cage using either radical- or palladium-mediated cyclization approaches, which could be initiated from either the back side or the front side of the cage-Uke structure. Four such scenarios are outlined in Figure 3. 

Transition metals, especially palladium, have been used for the stereoselective synthesis of these alkaloids with remarkable success. Since Overman s approach to (+)-tazettine (62) using an intramolecular Heck reaction (225), this methodology for the construction of the critical quaternary stereogenic center has been implemented for the preparation of many alkaloids. Grigg later reported access to (R,R)-crinane via regiospecific palladium-mediated cyclization (226). An efficient total synthesis of racemic galanthamine (75) following this approach has been recently disclosed (227). After the key intramolecular Heck reaction, deprotection of the... 

Zhang, H.-C. and Maryanoff, B.E. (1997) Construction of indole and benzofuran systems on the solid phase via palladium-mediated cyclizations. J. Org. Chem., 62,1804-9. 

The mechanism of this transformation has explored by Hashmi, and postulated to proceed via a Pd(II)/Pd(IV) cycle, wherein palladium mediates cyclization to form 14 (Scheme 6.23), followed by either proton migration and reductive elimination (forming simple furans) or allene coupling via either a carbene or insertion. This approach can be employed to form exclusively monomeric cydoisomerization products with more sterically encumbered substituted allenes [34]. 

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