Spirocycles, annulation

Figure 10.32 Applications of bidirectional chain extension for the synthesis of disaccharide mimetics and of annulated and spirocyclic oligosaccharide mimetics using tandem enzymatic aldol additions, including racemate resolution under thermodynamic control.

Ring expansion and concomitant chlorination of 1,3-dithiolanes with an enolisable methyl group occurs in DMSO on reaction with silica pre-treated with SOCI2, giving dihydro-1,4-dithiin derivatives. Spirocyclic dithioacetals yield the annulated dithiin <02JOC2572>. 

Palladium-catalyzed annulation reactions were involved in the syntheses of benzo[A furan-based spirocyclic compounds, 2-substituted-3-aroyl-benzo[A]furans, and 2-benzofuran-2-ylacetamides <07AGE7068 07JOC9278>. 

W.H. Moser and co-workers developed a new and efficient method for the stereocontrolled construction of spirocyclic compounds, including the spirocyclic core of the antitumor agent fredericamycin The strategy involved a one-pot aldol additioniBrook rearrangement cyclization sequence beginning from arene chromium tricarbonyl complexes and can formally be described as a [3+2] annulation. 

Moser, W. H., Zhang, J., Lecher, C. S., Frazier, T. L., Pink, M. Stereocontrolled [3 + 2] Annulations with Arene Chromium Tricarbonyl Complexes Construction of Spirocyclic Compounds Related to Fredericamycin A. Org. Lett. 2002,4, 1981-1984. 

Ring transformation of the isothiazolium salts can be converted into N-, O- and S-heterocycles, isothiazole derivatives, annulated isothiazoles and rearrangement products such as thiadiazapentalenes, spirocyclic isothiazolium salts and thianthrenes. 

Cyclization that eventualy places the resulting double bond endocyclic also occurs, as in the annulation of indoles and the formation of spirocyclic furanones and pyrrolones which involves a rearrangement process. ... 

Dienes coordinated to iron tricarbonyl do not undergo Diels-Alder reactions and a number of interesting annulation reactions of groups attached to iron tricarbonyl diene complexes have been developed. Cyclohexadiene iron tricarbonyl complexes having a pendant alkene undergo annulation reactions to form spirocyclic compounds (Scheme 160). Related reactions of allylic thioesters afford spirocyclic thialac-tones. 

Physical Properties of Benzothiazoles.—Dielectric relaxation studies on benzothiazole have enabled thermodynamic parameters to be determined. " Treatment of the diaryl sulphides (105 R = Me or Ph) with base gives the spirocyclic Meisenheimer complexes (106), which were identified by means of n.m.r. and visible spectroscopies, before rearranging to phenothiazine derivative. "" A "C n.m.r. study of 43 benzothiazole derivatives has given information concerning substituent effects on prototropic tautomerism and on annulation reactions. " Mass spectral studies have been reported on 2-acetamidobenzothiazole " and on some 2-(3 -aryl-5 -aminopyrazol-T-yl)benzothiazoles. " ... 

In an approach to the gastrin receptor antagonist (+)-AG-041, the Iwabuchi group has prepared the nitrogen-substituted spirocycle 153 by means of an oxidative intermolecular aza-spiro-annulation (Scheme 38) [82], Accordingly, indole 151 was treated with dirhodium catalyst 152 in the presence of PHl(OAc)2 and MgO to afford spirocycle 153 in 70% yield and 96% ee. The deuterium labeling was necessary for successful implementation of the spirocyclization. 

Various functional groups are tolerated and especially electron-withdrawing groups on the aryl halide appear to have a beneficial effect on the yields achieved (Scheme 19).[39],[40] Also, multiple annulated ring systems and spirocycles, which are related to drugs and natural products, are efficiently accessible by this methodology (Schemes 20a and... 

In 2012, the Chi group demonstrated a diastereoselective NHC-catalyzed access to p-lactam fused spirocyclic oxindoles with an all-carbon quaternary stereogenic center, employing oxindole-derived p,p-disubstituted a,p-unsaturated imines and enals as substrates. The p-lactam products, stable at room temperature, were easily converted to cyclopentenes at 50 °C. An asymmetric example of the annulation reaction was presented with moderate enantioselectivity (89% yield and 51% ee by using the amino indanol derived catalyst), which is probably due to the sterical hindrance of p,p-disubstituted a,p-unsaturated imines (Scheme 7.58). 

NHC-catalysed umpolung of enals appears to be a useful tool for annulation reactions that generally induces molecular complexity from simple starting materials. Enals have thus been reported as appropriate reaction partners for asymmetric annulation reactions with isatins and benzodi(enone)s to yield spirocyclic oxindolo-y-butyrolactones (121), and polycyclic compounds (122), respectively. Both annulation processes have been catalysed by chiral NHCs and accomplished in good yields with high regio- and/or stereo-selectivities. In parallel, the mechanism of the NHC-catalysed annulation reaction of butenal with pentenone has been computationally explored at the B3LYP/6-31+G and M06-2X/6-31G levels of theory. This study has clearly emphasized the key role played by proton-transfer steps in both the rate and the course of the reaction. 

Sames et al. developed an a-alkenylation of cycUc ethers to synthesize both annulation and spirocyclization products (Scheme 53) [39]. Four types of electronically diverse hydride donors were investigated and remarkably the selection of suitable catalysts was crucial to the success of cascade processes. As to substrate 137, in which relatively unreactive secondary C-H bond was exploited as hydride donor, no aromatic group was available to stabilize the oxocarbenium generated via [1,5]-HT. Hypervalent platinum catalyst Ptl4 was the optimal catalyst, which affected complete conversion of 137 to furnish the product 138 in 86 % yield, whereas Ptl4 only led to complete decomposition of 141 despite higher reactivity of... 

Jiang, K., Jia, Z.-J., Chen, S., Wu, L., Chen, Y.-C. (2010). Organocatalytic tandem reaction to construct six-membered spirocyclic oxindoles with multiple chiral centres through a formal [2-I-2-I-2] annulation. Chemistry — A European Journal, 16, 2852—2856. 

VCP 47 and CO underwent [5+1] annulation in the presence of a rhodium(I) catalyst to give cyclohexenone 48 (Scheme 2.41) [59]. Carbonylation of (cyclo-propylmethylene)cyclopropane 49 occurred with both Rh and Co carbonyl complexes to afford spirocyclic cyclohexenone 50 [60]. 

This strategy was used to synthesize spirocyclopenteneoxindoles, as well as stereodefined cyclopentenes. Likewise, Hu reported a [3 -f 2] annulation reaction of 2-atylideneindane-l,3-diones with MBH carbonates that proceeded smoothly in the presence of a multifunctional thiourea-phosphine catalysts to produce the corresponding quaternary carbon centered spirocyclic cyclopentenes. A phosphine-triggered tandem [3 + 4] annulation reaction between MBH carbonates and 1,4-diheteroatom dinucleophiles was described, which provided access to saturated seven-membered 1,4-heterocycles. Analogously, MBH carbonates were used as C3 synthons in asymmetric [3 + 2] annulation reactions for the asymmetric synthesis of 3-spirocyclopentene-2-oxindoles. Another kind of annulation reaction for the construction of highly functionalized stereodefined cyclopentene skeletons involved a Rauhut-Currier Domino Reaction. Finally, an efficient asymmetric [3 + 2] cycloaddition reaction between MBH carbonates of isatins and... 

---