Synthesis of Tricyclic Compounds

Holzapfel and coworkers [132] used the carbopalladation ofalkynes followed by a cyclization for the synthesis of tricyclic compounds as 6/1-280, derived from the sugar derivative 6/1-279 (Scheme 6/1.74). 

Scheme 6/1.74. Synthesis of tricyclic compounds from sugars.

More examples in this line can be found in the reports of Shea and Carbery. Perez-Gastells and co-workers combined ring-closure metathesis and PKR for the synthesis of tricyclic compounds in one batch. In this approach, a... 

Synthesis of tricyclic compounds containing a 4- to 7-membered heterocycle peri-annelated to a naphthalene system 90AHC(51)1. 

Our group has used a combined metathesis-PKR for the synthesis of tricyclic compounds in one step. The process starts from pure cobalt complexed dienynes 52. The cobalt cluster acts first as a protecting group to avoid undesired enyne metathesis processes. The methodology allows the formation of tricyclic [6.5.5] (53) and [7.5.5] (54) structures including, in some examples, oxygen or nitrogen. Tricycles 53 are obtained in a total stereoselective manner, while compounds 54 are formed as mixtures of two diastereomers (Scheme 17) [110]. 

Scheme 17 Tandem RCM-PKR for the synthesis of tricyclic compounds in one step...

The synthesis of tricyclic compounds based on the cyclisation of methyl geranyl-geranoate was described eighteen years ago. However, the discovery of expoxy-squalene as an intermediate in steroid biosynthesis, and the corresponding in vitro cyclisation experiments, have re-awoken interest in this area of diterpene synthesis. The structural and stereochemical course of the in vitro cyclisation of the epoxy-trans-olefin (138) has been studied. Two A/B-trans-fused tricyclic compounds (139) and (140) have been isolated. The levantenolides (142) and (143) have been obtained by two closely related routes. In the first, the butenolide (141), derived from monocyclofamesyl bromide, afforded the a- and P levantenolides (142) and (143) on cyclisation with stannic chloride. In the second, the corresponding acyclic butenolide derived from famesyl bromide was cyclised. 

Application of a general synthesis of 4-hydroxycoumarins allowed the synthesis of tricyclic compound (30) from ester (29) (Equation (5)) <86UKZ1082>. 

Thiaisatoic anhydrides have been considered as precursors for the synthesis of tricyclic compounds containing thiophene ring. Syntheses of these anhydrides have a major problem owing to the instability of their precursors thiophene o-aminoacids, which easily decarboxylate at room temperature. Under MWI, alkaline hydrolysis of... 

An asymmetric synthesis of tricyclic compounds through the desym-metrization of cyclohexadienones was developed to provide a wide variety of cyclohexadienones with tetrahydrofuran motifs via a [4 + 2] cycloaddition (14AGE8184). 

The Claisen-Johnson rearrangement is also a reaction of choice for the construction of quaternary centers in the synthesis of triquinanes and related ter-penes. Accordingly, transposition of aUyUc alcohol 125 is a cornerstone reaction in the synthesis of tricyclic compound 124, a key intermediate for the access to several triquinanes described by Iwata [28] (Scheme 6.17). Acid 126 was obtained in 57% yield after transposition and saponification. Claisen allyl vinyl ether rearrangement was also applied to allylic alcohol 125. Oxidation of the aldehyde inter-... 

Enders described a fascinating organocatalytic one-pot asymmetric synthesis of tricyclic compounds using a triple-cascade/Diels-Alder reaction sequence. Combination of dieneal 110 with enal 111 and nitro alkene 112 in the presence of a chiral amine catalyst results in a Michael/Michael/aldol condensation sequence to yield cycloaddition precursor 113. Cooling the reaction mixture and addition of a Lewis acid promotes the desired intramolecular Diels-Alder reaction to selectively afford the highly functionalized tricyclic target 114. ... 

Compared to the example above, the participation of benzene in the aromatic-Cope rearrangement has been more difficult to achieve. However, it has recently been utilized for the preparation of helicenes and other polycyclic compounds.One of the first and most impressive demonstrations of this reaction was utilized in the synthesis of tricyclic compounds such as 252. As above, the anionic oxy-aromatic-Cope rearrangement of 251 proceeded in excellent yield to give 252, resulting from rearomatization of the benzene ring. 

The combination of a Diels-Alder reaction with subsequent enamine-catalyzed Michael addition has been described for the synthesis of tricyclic compounds, precursors of natural products such as penicillone A [45]. Application to ketones has been successfully achieved with the elegant synthesis of (-)-minovincine based on a Diels-Alder/Michael organocascade (Scheme 7.28) [46]. 

The synthesis of tricyclic compound 120 was first reported by Tamura and co-workers using a tandem transesterification-cycloaddition reaction of nitrone methyl ester 118 and cyclohexen-3-ol (Scheme 16.17). This reaction was catalyzed by titanium tetrachloride to make nitrone cyclohexenyl ester 119. A subsequent 1,3-dipolar cycloaddition reaction proceeded presumably through a transition state involving the i-cis-like conformation of the ester C—O bond and the E configuration of the nitrone C=N bond (Scheme 16.17). 

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