Rearrangements variant

Scheme 21 Examples of cyclopropyl methyl radical rearrangement variants...

It should be noted that the 2-oxazolines are connected directly with enamides, being their products of cyclization on the one hand ", as well as being the heterocyclic precursors of W-acylenamines on the other . However, it is no less important that the 2-oxazolines are cyclic derivatives (and precursors also) of the 1,2-aminoalcohols. In essence, the reactions 117 122 (equation 41) and 125- 128 (equation 43) are the transformations of ketones to 1,2-aminoalcohols, i.e. they are the reversal of one of the pinacol rearrangement variants, i.e. the Tiffeneau and MacKenzie reactions . These transformations which proceed via the iV-acyliminium intermediates 118, 126 are examples of a real retropinacol rearrangement according to structural, functional and redox features (see Section III.B.3). 

The most widely used variant of the Gabriel-Colman is the conversion of saccharine derivatives to benzothiazine derivatives. The reaction has been extensively studied as benzothiazines are important pharmacophores, particularly in the oxicam class of antiinflammatories. The first reported instance of this transformation was in 1956 where 43 was treated with sodium methoxide to provide 44. The rearrangement also works with esters " and some amides " in addition to ketones. 

A variant is represented by the benzilic ester rearrangement, where an alkoxide is used as nucleophile. The alkoxide should not be sensitive towards oxidation. The reaction product is the corresponding benzilic acid ester 5 ... 

An important variant is the rearrangement of silylketene acetals like 10 and 11 which are easily accessible from allyl esters 9. This so-called Ireland-Claisen rearrangement is a valuable carbon-carbon bond forming reaction that takes advantage of the fact that the reactants are first connected to each other by an ester linkage as in allyl esters 9, that are easy prepare. 

A related reaction is the oxa-di-n-methane rearrangement, where one of the C=C double bonds is replaced by a C=0 double bond. The substrates are thus /3,y-unsaturated ketones. The rearrangement proceeds from the triplet state. This oxa-variant gives access to highly strained molecules containing small rings, as has been demonstrated by irradiation of norborn-5-ene-2-one 10 ... 

A photochemical variant, the so-called photo-Fries rearrangement, proceeds via intermediate formation of radical species. Upon irradiation the phenyl ester molecules (1) are promoted into an excited state 11. By homolytic bond cleavage the radical-pair 12 is formed that reacts to the semiquinone 13, which in turn tautomerizes to the p-acylphenol 3. The corresponding ort/zo-derivative is formed in an analogous way ... 

Generally yields are good. R can be alkyl or aryl. Modern variants of the Hofmann rearrangement use lead tetraacetate" or iodosobenzene instead of hypo-bromite. 

The vinylcyclopropane rearrangement is of synthetic importance, as well as of mechanistic interest—i.e. the concerted vs. the radical mechanism. A reaction temperature of 200 to 400 °C is usually required for the rearrangement however, depending on substrate structure, the required reaction temperature may range from 50 to 600 °C. Photochemical and transition metal catalyzed variants are known that do not require high temperatures. 

A salient structural feature of intermediate 18 (Scheme 2b), the retrosynthetic precursor of aldehyde 13, is its y,r5-unsaturated ester moiety. As it turns out, the Johnson ortho ester variant of the Clai-sen rearrangement is an excellent method for the synthesis of y,<5-unsaturated esters.11 In fact, the Claisen rearrangement, its many variants included, is particularly valuable in organic synthesis as a method for the stereocontrolled construction of trans di- and tri-substituted carbon-carbon double bonds.12,13 Thus, it is conceivable that intermediate 18 could be fashioned in one step from allylic alcohol 20 through a Johnson ortho ester Claisen rearrangement. In... 

Scheme 1. Parent Claisen rearrangement (a) and the Johnson ortho ester variant (b).

P-citronellene 605 f 612 (/Q-citronellic acid 232, 235 (/ )-citronellol 360 Claisen rearrangement 17, 87, 90, 137 f., 140, 142, 194 -, Johnson ortho ester variant see Johnson ortho ester Claisen rearrangement cobalt-mediated cyclization... 

A variant of Method B is the cyclization of the phenolic 2-(chloroacetamido)benzophenones 9, produced by photo-Fries rearrangement (see Houben-Weyl, Vol. 7/2a, p 1148 ff) of the esters 8, with ammonia via the corresponding iodoacetyl compounds.195... 

A. Claisen Rerrangements of Ketene Aminats and Imidates. A reaction that is related to the orthoester Claisen rearrangement utilizes an amide acetal, such as dimethylacetamide dimethyl acetal, in the exchange reaction with allylic alcohols.257 The products are y, 8-unsaturated amides. The stereochemistry of the reaction is analogous to the other variants of the Claisen rearrangement.258... 

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