Annulation strategy

A more recent ring annulation strategy for the total synthesis of steroids from the Stork group is shown in the following equation (210 — 211 — ... 

Scheme 36. Piers s annulation strategy based on the intramolecular Stille reaction.

Scheme 2.102. Natural products available through the [3+2] annulation strategy.

We commenced our own approach toward ( )-phomactin A with an intent to feature an oxa-[3 + 3] annulation strategy [24—28] that was developed in our lab [29-32] and, in particular, an intramolecular annulation. While oxa-[3 + 3] annulations or related reaction manifolds [33, 34] are known and can be traced back more than six decades [35], an intramolecular variants of this reaction were not known [24—28]. There were no applications of intramolecular oxa-[3 + 3] annulations in natural product synthesis [27, 28, 36] until our approach toward phomactin A was disclosed. Subsequently, an account toward ( )-likonide B was reported by Trauner [36e],... 

Wender et al. s [5 + 2] metal-catalyzed annulation strategy has also been applied to the total synthesis of (+)-aphanamol I (154) [34]. The scope of this method was expanded by using a tetrasubstituted allene that resulted in the stereoselective formation of an angular methyl group. The reaction of allene 149 with 0.5 mol% of rhodium biscarbonyl choride dimer afforded the fused bicyclic product 152 in 93% yield with complete exo/endo and diastereoselectivity (Scheme 19.28). The stereoselectivity of this process was attributed to a preference for formation of the cis-fused metallo-... 

Marino and his coworkers [20a], on the other hand, studied the fluoride ion-induced desilylation of ethyl 2-silyloxycyclopanecarboxylates 24 and the resulting "homoenolate" anion 25 was allowed to react with different electrophiles, such as Michael acceptors, to give dissonant cyclopentene rings (26) via a [3 -i- 2] annulation strategy (Scheme 5.16). 

On the basis of their earlier aromatic annulation strategy (see Scheme 5.64) (596), Shin and Ogasawara reported the first enantioselective total synthesis of carbazo-quinocins A (272) and D (275) (639). The required methyl-substituted secondary chiral stereogenic center of the alkyl side chain at C-1 of carbazoquinocins A and D was introduced starting from the O-benzyl (R)-glycidol (R)-897. 

Gribble et al. also reported a new annulation strategy for the total synthesis of ellipticine (228) (527). This methodology utilizes a Diels-Alder reaction between... 

Kocienski, P. J. Pontiroli, A. Qun, L. Enan-tiospecific syntheses of pseudopterosin agly-cones. Part 2. Synthesis of pseudopterosin K-L aglycone and pseudopterosin A-F agly-cone via a B-BA-BAC annulation strategy. 

The basic fraction of the ethanolic leaf extract of the Malaysian plant Kopsia griffithii exhibits a strong antileishmania activity. One of the two novel alkaloids isolated from this plant in 1998 was the indolizidino[8,7-fo]indole harmicine [17]. Synthetic approaches to harmicine became attractive owing to its pharmacological potential [18,19]. We applied our three-step pyrrolidine annulation strategy to the synthesis of harmicine (Scheme 15.5) [19]. 

Further studies on the scope and stereochemical course of the oxyanion-accelerated vinylcyclopropane reairangement were reported in 1981. This paper introduced a general [4+1] annulation strategy for the synthesis of cyclopentene derivatives in which the anion-accelerated VCP rearrangement functions as the key step. In this report, the accelerated version of the vinylcyclopropane rearrangement was also shown to proceed with remarkably high stereoselectivity, in further contrast to the thermal process. 

A related [4 + 4] annulation strategy relies on the base-promoted l,4-dehydrochlc ination of a,p-un-saturated acid chlorides the transformation outlined in Scheme 29 (reported by Dreiding and cowor-kers) illustrates this approach. In some cases it is possible to effect all three steps — ketene generation, [2 + 2] cycloaddition, and Cope rearrangement — in a single synthetic operation. ... 

Davies, H. M. L., Doan, B. D. Total Synthesis of ( )-Tremulenolide A and ( )-Tremulenediol Avia a Stereoselective Cyclopropanation/Cope Rearrangement Annulation Strategy. J. Org. Chem. 1998, 63, 657-660. 

Cyclopentene derivatives with unsaturated appendages are also available via this general annulation strategy representative examples are presented in Scheme 15. In these several transformations desulfonylation is achieved using base-induced -elimination, via the fluoride-promoted elimination of 3-silyl sulfones, and by means of Brook rearrangement chemistry according to the method of Reich. In summary, a wide variety of complex functionalized cyclopentenes are available using this versatile [4 1]... 

Strategy C in Scheme 21 employs the [2 + 2] cycloaddition of vinylketenes and 1,3-dienes to generate the requisite 2-vinylcyclobutanone intermediates for oxyanion-accelerated VCB rearrangement. The sequence presented in Scheme 23 illustrates this two-step [4 + 2] annulation strategy, the overall result of... 

The first non-racemic synthesis of dactylol was demonstrated by Molander and Eastwood using a 5+3 annulation strategy (Scheme 5). In... 

A controlled crisscross annulation strategy has been used to construct the eight-membered ring compound (457) has been prepared in five steps. The key reaction was conducted under electrolytic reduction conditions to afford the benzazocine derivative (458), which was transformed to (459) in 20 steps. Oxidation of the alcohol and further treatment with /-butyldimethylsilyltriflate gave the tricyclic compound (460) (Scheme 32) <88JOC5355>. 

Feldman and coworkers have generated radicals from vinylcyclopropanes in the presence of thiyl radicals and studied their reaction with alkynes to give vinylcyclopentenes. A general [3+2] annulation strategy considers vinylcyclopropanes 39 as the three atom components and alkynes 40 as the two atom counterparts (Scheme 14). The vinylcyclopentene products have been obtained as mixtures of syn- and a /-substituted stereoisomers the authors considered that product stereochemistry is set during the cyclization of the 5-hexadienyl radical 41 and derives from the two conformations (chair- or boat-like) in the transition state. 

This aromatic annulation strategy has been successfully applied in an efficient total synthesis of the antitumor antibiotic mycophenolic acid. ... 

This imine annulation strategy has been extended to the synthesis of and y-carbolines, where facile thermal cyclization during imine formation has been observed (Eq. 21) [54,55]. 

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