Ferrier-type reactions

Diacetyl-L-rhamnal underwent a Ferrier-type reaction with silylated uracil and thymine to give the 2, 3 -unsaturated nucleosides. ... 

Scheme 45. Aluminum-mediated carbocyclizations Ferrier-type reaction vs. Claisen rearrangement [77]...

Reactions with Carbohydrates. AgOTf and MoCl2(acac)2 combine to form a catalyst that has been utilized in allylic substitution reactions with glycals, versatile building blocks of carbohydrate chemistry, to give Ferrier-type reaction products (eqs 26 and 27). 

In synthetic studies of gleosporone, an autoinhibitor of spore germination, Schreiber reported a highly stereoselective Ferrier-type reaction of cyclic enol ether 77 (Scheme 1.10) [29]. It is likely that minimization of A, 3 interactions in the cyclic oxonium intermediate (cf. 79) is the controlling feature in this diastereoselective process. 

This methodology has been used for the synthesis of the C3-C14 segment 24 of the antitumor agent laulimalide 23 (Scheme 4.22) [35]. The constrained chiral BOX ligand 21c in combination with Cu(OTf)2 afforded dihydropyrane 6f by a cycloaddition reaction in good yield and ee this was converted to the C3-C14 segment 24 via a Ferrier-type rearrangement in several steps. 

Ferrier-type rearrangement to give glycal 74 [25] (Scheme 18). Spiroketals 75 are then obtained after desilylation. A similar sequence of reactions based on cyclic sulfate 76 furnishes adduct 77 which, after desilylation to give 78, provides spiroketals 79 upon N-iodosuccinimide (NIS) treatment. 

In order to simplify these preparations, Boivin et al. [52] made use of the allylic rearrangement reaction (Ferrier type) which was one of the first accesses to 3-amino glycals. By use of azide as the nucleophile, the L-arabino configurated glycal 78... 

The Ferrier (II) reaction is quite efficient to form six membered carbocycles, but is unsuitable to prepare cyclopentitols. Five membered enollactone 14 was converted to the cyclopentanone derivative 16 as a single epimer upon treatment by LiAlH(OtBu)3 (Scheme 4) [41]. Spectroscopic studies established some mechanistic details. Accordingly, the hydride of the reducing agent rapidly added to the carbonyl and formed with the metal a stable alu-minate complex. The carbocydization occurred by protonation followed by fragmentation and aldol type cyclization process. 

From the retrosynthetic perspective (Fig. 2), the tetracyclic structure is expected to be accessible by tandem Michael-Dieckmann type reaction of 59 with 60. The suitably substituted chiral intermediate 59 would be synthesized by Diels-Alder reaction of the cyclohexenone 57 and the silyloxybutadiene 58. The regio- and stereoselectivities are established as a consequence of the dienophile geometry according to Gleiter s theory (29). Compound 57 could be obtained from 51 through Ferrier reaction of 54. 

Ferrier-type rearrangement,or Perrier reaction, but is called the Perrier reaction in this book to differentiate it from another type of rearrangement also developed by Perrier and co-workers. 

The proposed mechanism of the Ferrier carbocyclization reaction is oudined in Scheme 12.13. First, oxymercuration of the exo-olefin in 48 affords mercurial-hemiacetal 49, whose aglycon moiety (-OMe) eliminates to give mercurial-aldehyde derivative 50. This mercurial intermediate 50 was isolable when a stoichiometric amount of Hg salt was employed at low temperature. Intramolecular aldol-type cyclization of 50 provides product 51. 

Chiral cyclohexanones obtained by the Ferrier carbocyclization reaction are useful precursors for the synthesis of cyclitols and aminocyclitols, some of which are found in clinically important aminoglycoside antibiotics. Additionally, highly substituted cyclohexenones, prepared by the Ferrier carbocyclization followed by (3-elimination, can undergo various further transformations, also making these compounds potential chiral building blocks for the preparation of structurally complex compounds having cyclohexane unit(s). This section provides an overview of the reported synthetic strategies toward various types of natural products based on utilization of the Ferrier carbocyclization reaction. 

Only very recently [77], Sinay et al. presented a series of Ferrier-type rearrangements [78] of 5,6-unsaturated sugars to cyclohexenones. In this study, the same catalyst, applied to the reaction of furanyl C-glycoside 216, yielded exclusively, after reduction of the intermediate ketone, cyclohexanol 217 (Scheme 45). A conceivable Claisen rearrangement to a bicyclic product 218 was apparently not observed. 

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