Carbon Ferrier reaction

Research in the laboratory of H.M.I. Osborn showed that the use of cyclohexene derivatives as nucleophiles in the Lewis acid-mediated Type I carbon-Ferrier reaction of 3-0-acetylated glycals can be used to prepare unsaturated 3-linked C-disaccharides. The incorporation of the alkene took place with one equivalent of glucal in the presence of boron-trifluoride etherate in 33% yield. The desired C-disaccharide was obtained by selective hydrogenation of the exocyclic double bond in the presence of an endocyclic one. 

D.R. Williams and co-workers accomplished the first total synthesis of marine dolabellane diterpene (+)-4,5-deoxyneodolabelline. The Type I carbon-Ferrier reaction was utilized to assemble the key frans-2,6-disubstituted dihydropyran with complete stereoselectivity (a-anomer). The macrocyclization was carried out with a vanadium-based pinacoi coupiing. 

Scheme 5.2-99 The Carbon-Ferrier reaction in [BMiM][BF4] and [BMIM][PF6] [229],...

The Carbon-Ferrier reaction involves the addition of an allylsilane or silyl-enol ether to a dihydropyran. This was found to occur in the ionic liquids [BMIM][Bp4] and [BMIM][rf2N] using Yb(OTf)3 as a catalyst [229]. The reactions typically gave 80% yield for the reactions of allyl silanes and 60% yield for the reactions with TMS enol-ethers (Scheme 5.2-99). 

Finally a unique approach starting at ring A was presented by the introduction of the C25 substituent of avermectin B via carbon-Ferrier technology [33]. Thus reaction of D-glucal derivative 12 with Z-triphenylcrotylsilane displaced a pivalate group and sets up another pivalate displacement via 13 by dimethylcuprate to introduce the C24 methyl group and positioned the double bond exactly where required for avermectin B. The other unique feature of this route is the oxidative cyclization of a hydroxyl function onto a dihydropyran to effect spiroketalization. 

This and previous results are in accord with the finding of Lukacs et al. [55, 56] that an apparent relationship between the stereochemistry at the C5 carbon of the cyclohexanone derivatives produced in the Ferrier reaction and the conformation of... 

The synthetic plan for an antitumor alkaloid, lycoricidine 64, based on the Ferrier carbocyclization is shown in Scheme 12.18. The tricyclic phenanthridone skeleton was envisioned to be constructed by C—C bond formation between C-lOa and C-lOb by a transition metal-catalyzed sp -sp carbon coupling reaction. The C-ring 65 possessing an... 

The most efficient photosubstitution reaction, with many applications in synthesis, is the photobromination method developed by FERRIER s group [24]. The substitution of H-5 is regioselective and stereoselective for pentopyranosides [25], hexo-pyranosides [26], 1-6 anhydrosugars [27], uronic acids [24, 28] heterocyclic derivatives from deoxyinosones [29], nucleosides [30, 31], etc.. . using bromine or N-bromo-succinimide in carbon tetracloride under irradiation. 

The Ferrier carbocyclization reaction is a reliable transformation of 5-enopyranosides into carbocycles. As shown in Scheme 12.12 (the carbon numberings in substrates and products have been changed the numbering of substrates is based on the nomenclature of carbohydrates, and the numbering of products is that of cyclohexanones), irrespective of the kinds of substituents and patterns of stereochemistry in the substrates, the rearranged products (15 and 42-46) were obtained in moderate to good yields with relatively high diastereoselectivity. An exception is a reaction of a 4-deoxy-5-enopyranoside derivative, which resulted in a low yield of product 47. 

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