Chelation-controlled rearrangement

Enolates of allyl esters of a-amino acids are also subject to chelation-controlled Claisen rearrangement.249... 

Scheme 2.44 Chelate-controlled Claisen rearrangement of zinc ester enolates 136. Cbz = benzyloxycarbonyl Boc = tert-butoxycarbonyl.

Further variations of the Claisen rearrangement protocol were also utilized for the synthesis of allenic amino acid derivatives. Whereas the Ireland-Claisen rearrangement led to unsatisfactory results [133b], a number of variously substituted a-allenic a-amino acids were prepared by Kazmaier [135] by chelate-controlled Claisen rearrangement of ester enolates (Scheme 18.47). For example, deprotonation of the propargylic ester 147 with 2 equiv. of lithium diisopropylamide and transmetallation with zinc chloride furnished the chelate complex 148, which underwent a highly syn-stereoselective rearrangement to the amino acid derivative 149. 

Scheme 18.47 Synthesis of the allenic amino acid derivative 149 by chelate-controlled Claisen rearrangement [135] (LDA= lithium diisopropylamide Cbz = benzyloxycarbonyl).

On the other hand, a double asymmetric version where both radical fragments are chiral has been investigated (equation 12) . The stereochemistry of the rearrangement products 20a and 20b is not the result of chelation control, but is determined by the stereochemistry of the hthium-bearing terminus. The significant difference in the stereospecificity of 19a and 19b reveals that a substantial level of mutal recognition of the radical enantiomers takes place during the recombination process. 

Polyols synthesis A two-directional application of chelation-controlled [1,2]-Wittig rearrangement has been used to prepare the all syn polyol 31 from 30 (equation 16) °. 

The highly selective addition was rationalized by a chelation control as shown in equation 8. Tetracoordinate organolithium can form complexes 16a and 16b with the chiral oxazoline. The addition, which can be viewed as a suprafacial 1,5-sigmatropic rearrangement, proceeds from 16b where the C—Li bond is parallel to the 7T-orbital of the naphthalene ring. The attack of an electrophile on the azaenolate 17 formed by the... 

An aromatic Claisen rearrangement has been used as a key step in a total synthesis of racemic heliannuols C and E.18 A formal synthesis of (-)-perhydrohistrionicotoxin has used Claisen rearrangement of an amino acid ester enolate as the key step, in which almost total chirality transfer was observed from (S, )-oct-3-en-2-ol in the sense predicted by a chair-shaped transition state with chelation control of enolate geometry.19 Treatment of 1-(cyclohex-l-enyl)-6-methoxy-2-propargylindanol derivatives with base... 

A recent application of the furan-carbonyl photocycloaddition involved the synthesis of the mycotoxin asteltoxin (147)." Scheme 16 shows the synthetic procedure that began with the photoaddition of 3,4-dimethylfuran and p-benzyloxypropanal to furnish photoaldol (148), which was epoxidized with MCPBA to afford the functionalized product (149) in 50% overall yield. Hydrolysis (THF, 3N HCl) provided the monocyclic hemiacetal which was protected as its hydrazone (150). Chelation-controlled addition of ethylmagnesium bromide to the latent a-hydroxy aldehyde (150) and acetonide formation produced compound (151), which was transformed through routine operations to aldehyde (152). Chelation-controlled addition of the lithium salt of pentadienyl sulfoxide (153) followed by double 2,3-sigma-tropic rearrangement provided (154) as a 3 1 mixture of isomers (Scheme 17). Acid-catalyzed cyclization of (154) (CSA/CH2CI2) gave the bicyclic acetal (155), which was transformed in several steps to ( )-asteltoxin (147). ... 

Development of a novel route to the C-7 to C-13 portion e.g. 122) of erythronolides A and B (i.e. 121a and 121b) by Burke makes use of a stereoselective addition of an isopropenyllithium-derived cuprate to homochiral aldehyde (123) as a first, key step (Scheme 20). Formation of allylic alcohol (124) as the major product presumably reflects a 3 chelation controlled pathway vide supra) Subsequent handling of (124), which included as the second critical step a dioxanone to dihydropyran enolate Claisen rearrangement, produces three key subunits, including (122). 

Scheme 2 Chelation-controlled 1,2-rearrangement of glyceryl allyl ethers...

Claisen rearrangement. The enolate Claisen rearrangement of allyl esters of dipeptides is under chelation control by the addition of MnClj. 

Cyclic Transition States chelation control, reagent delivery, rearrangements. 

Chelation-controlled Claisen rearrangements are also tolerant to lietero substituents in the /3-position of the allylic moiety. 

Table 15. Chelation-Controlled Claisen Rearrangement of Vinylsilane Derivatives498...

The stereochemical course of 1,2 rearrangements is comparable to chelation-controlled rearrangements (see p 3420), and the chairlike transition state predominates. Despite the fixed vinyl double-bond geometry, however, the stereochemical outcome from these reactions indicates more or less intermediacy of the boatlike geometry, as observed in ortho ester rearrangements520- 52 h... 

Better results are obtained in chelation-controlled rearrangements of (E)- or (Z)-derivatives 3592. These rearrangements proceed with known internal asymmetric induction [e.g., anti for the ( -substrate because of the change in the chain see Section 1.6.3.1.1.4.], and with respect to the relative asymmetric induction the syn relationship is preferred. 

In contrast to chelation-controlled anionic Claisen rearrangements of /(-hydroxy esters [where chelation control only allows the formation of (i -lithium enolates see p 3420], all four diastereomeric A-crotylic a-hydroxy ketene dithioacetals can be prepared either by deprotona-... 

Diastereoselectivities in the range d.r. 92 8-95 5 were obtained in the chelation-controlled ester enolate rearrangements of propargyl glycolates 7. The major diastereomers 11 probably arise via the less hindered transition state 10672. 

Honda and his co-workers synthesised methyl (+)-nonactate 179, setting up the C-6 to C-8 relationship by a chelation controlled allylsilane reaction on the aldehyde 169, and the C-3 centre by hydrogenation of the dehydro intermediate 176 carrying two methoxycarbonyl groups (37) (Scheme 24). The thiolactone 175 and dimethyl diazomalonate gave the dehydro intermediate 176 in the presence of dirhodium tetraacetate, by way of a sulfur-ylid rearrangement developed by these... 

In a second chelation-controlled addition, 286 is converted to 287 by addition of Grignard reagent to the acetyl carbonyl (80 1 diastereoselectivity) followed by lactonization. Di-oxanone-dihydropyran Claisen rearrangement (287- 288) establishes the desired carbon skeleton. It is ironic that the original (iS)-lactate stereocenter, which was responsible for all the stereochemistry, is ultimately destroyed in 289. An additional 11 steps is required to reach the target C-7 to C-13 fragment [103]. 

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