Eight-membered ring annulation

A notable eight-membered ring annulation was reported by Echavarren et al. in their study of indoles as substrates for the intramolecular reaction [134]. 

Tautens and co-workers subsequently extended this methodology to the functionalization of other heteroarenes and to eight-membered ring-annulated indoles, even though with lower yields than their six- and seven-membered counterparts (08JOC1888). 

Holt and co-workers applied their ring-closing metathesis strategy for the synthesis of six-, seven-, and eight-membered ring annulated carbohydrate systems to synthesize a number of enantiomerically pure annulated carbohydrate systems containing nine-membered ring... 

The novel [6+2] annulation approach developed by the Takeda group has also been included in a threefold anionic/pericyclic process (Scheme 2.149) [340]. The reaction leads to functionalized eight-membered rings 2-659 in a highly stereoselective manner, starting from acylsilanes 2-656 and 3-(trimethylsilyl)vinyl-lithium (2-657). After 1,2-addition and 1,2-Brook rearrangement, the cyclobutane 2-... 

An eight-membered ring was annulated to pyrimidines by reaction of /ram-2,2 -dichlorodicyclohexylsuI lide with uracil derivatives in DMSO in the presence of phase-transfer catalyst (Equation 27 <2002ZPK1309, 2004MI1213>). 

The process has also been extended to the X = C series. The ring expansion-cyclopentane annulation provides good yields for the five- to six- (82%), six- to seven- (90%) and seven- to eight-membered ring (75%) ketone series studied (Scheme 74 equations 32 and 33). ... 

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>. 

The first example in Scheme 5.23 stems from the ( )-duocarmycin S A (127) synthesis by Natsume and coworkers [59] cyclization of 125 provided the expected product 126 in 82% yield along with 11% the isomeric enamine (not shown) (125 126, Scheme 5.23). In the Mizoroki-Heck reaction of 128, an eight-membered ring was exclusively tra 5-annulated in 64% yield, resembling a steroid-like polycyclic structure (128 129) [45, 60]. 

Larock s group studied the application of palladium catalysts in the ear-bonylative annulation of internal allqmes with 2-iodobenzyl alcohols. Seven- and eight-membered ring lactones were synthesized and the scope and limitations of the process were examined. With a lower reaction temperature, non-alkyne-inserted phthalides were produced. 

Eight-membered rings are less commonly prepared by annulative RCM, with a number of reports of failure. Medium ring synthesis by RCM is often challenging, and has been the topic of a number of reviews. Grubbs reported the failure of dienes 108 and 109 to undergo RCM when conducted at an initial substrate concentration of 10 mmol (Scheme 2.43) the em-diester functionality is therefore not sufficient to achieve selective cyclization at this reaction concentration. Instead, dimeric species 110 and 111 were isolated and characterized, indicating that the EM was very low the EM is likely to be below 1 mmol as the desired cyclooctene products... 

Murakami M, Ashida S, Matsuda T (2006) Eight-membered ring construction by [4+2+2] annulation involving p-carbon elimination. J Am Chem Soc 128(7) 2166-2167. doi 10.1021/... 

Higher cycloaddition reactions, using VCPs as the five-carbon unit, have also been developed. Rhodium-catalyzed carbonylation of VCP-enes resulted in [5+2+1] annulation to furnish eight-membered ring enones (Scheme 2.46) [66]. 

Intramolecular [6-1-2] annulation of 2-vinylcyclobutanone and alkene produced the eight-membered ring ketone 19 (Scheme 3.6) [18]. 

The reaction of cyclobutanone 58 with the diyne 62 resulted in [4+2+2] annulation to produce the bicyclic eight-membered ring ketone 63 (Scheme 3.36) [46]. The substrate scope was good, wherein different combinations of cyclobutanone... 

Syntheses of eight-membered rings are rapidly becoming of paramount importance in many laboratories, and one new approach involves a [4 + 4] annulation involving 1,3-dienes and vinylketene (derived from cyclobutenone). The initially formed 2,3-divinylcyclobutanone (203) undergoes a [3+3]... 

Formation of Eight-Membered Ring Systems by [4+2+2] Annulation... 

Murakami, M., Ashida, S. and Matsuda, T. (2006) Eight-membered ring construction by [4-I-2-I-2] annulation involving beta-carbon elimination./o r d/ of the American Chemical Society, 128(7), 2166-2167. 

Molander, G. A. Kollner, C. Development of a protocol for eight- and nine-membered ring 488 synthesis in the annulation of sp2,sp3-hybrid-ized organic dihalides with keto esters. /. Org. Chem. 2000, 65, 8333-8339. 

This is confirmed by a very similar homologous germylene compound [85] that has two annulated quinoxaline units on an eight-membered germylene ring system. There, the germanium centre is sufficiently electron deficient to ligate a chloride anion, i.e. it acts as an electrophile not as a nucleophile. 

In the laboratory of S.L. Schreiber, the total synthesis of (+)-epoxydictymene was accomplished by the tandem use of cobalt-mediated reactions as key steps. The eight-membered carbocycle was formed via a Nicholas reaction, while the five-membered ring was annulated by the Pauson-Khand reaction. Several P.-K. conditions were explored and the best diastereoselectivity was observed when NMO was used as a promoter. The annulated product was isolated as an 11 1 mixture of diastereomers. 

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