Cope rearrangement chirality

Keywords Aza-Claisen rearrangement 3-Aza-Cope rearrangement Chirality transfer Asymmetric induction Charge acceleration... 

The transposition of oxygen in allylic esters (R6 = alkyl, phenyl) or carbamates [R6 = N(CH3)2] has the same overall bonding changes as the thermal [3,3] sigmatropic Claisen or Cope rearrangements. Chirality transfer from C-l to C-3 is accompanied by 1,3 oxygen transposition (carbonyl O to allylic O ). 

The Rh2(DOSP)4 catalysts (6b) of Davies have proven to be remarkably effective for highly enantioselective cydopropanation reactions of aryl- and vinyl-diazoacetates [2]. The discovery that enantiocontrol could be enhanced when reactions were performed in pentane [35] added advantages that could be attributed to the solvent-directed orientation of chiral attachments of the ligand carboxylates [59]. In addition to the synthesis of (+)-sertraline (1) [6], the uses of this methodology have been extended to the construction of cyclopropane amino acids (Eq. 3) [35], the synthesis of tricyclic systems such as 22 (Eq. 4) [60], and, as an example of tandem cyclopropanation-Cope rearrangement, an efficient asymmetric synthesis of epi-tremulane 23 (Eq. 5) [61]. 

Scheme 10 Diaza-Cope rearrangement of chiral 2,5-diaza-1,5-dienes and homolytic C - C bond cleavage of dimetal piperazides cause loss of stereochemical pimity...

Scheme 6.13 gives some examples of Cope and oxy-Cope rearrangements. Entry 1 shows a reaction that was done to compare the energy of chair and boat TSs. The chiral diastereomer shown can react through a chair TS and has a AG about 8 kcal/mol lower than the meso isomer, which must react through a boat TS. The equilibrium is biased toward product by the fact that the double bonds in the product are more highly substituted, and therefore more stable, than those in the reactant. 

The Davies group has described several examples of a rhodium-catalyzed decomposition of a diazo-compound followed by a [2+1] cycloaddition to give divinyl cyclopropanes, which then can undergo a Cope rearrangement. Reaction of the pyrrol derivative 6/2-51 and the diazo compound 6/2-52 led to the tropane nucleus 6/2-54 via the cyclopropane derivative 6/2-53 (Scheme 6/2.11) [201]. Using (S)-lactate and (R)-pari lolaclorie as chiral auxiliaries at the diazo compound, a diastereoselectivity of around 90 10 could be achieved in both cases. 

Transformation of the 7-oxo-2-enimides 28, available from chiral syn-aldols by a Cope rearrangement, into enantiopure tetrahydropyrans involves reduction of the aldehyde function followed by a fast intramolecular oxa Michael addition. The stereochemical course of the... 

Stereocontrolled oxy-Cope rearrangement. 1,2-Addition of a chiral vinyl-lithium reagent to a chiral (3,-y-unsaturated ketone could give rise to at least eight... 

An irreversible consecutive reaction as a driving force to shift an unfavorable Cope rearrangement equilibria in the needed direction can be illustrated by the Cope-Claisen tandem process used for the synthesis of chiral natural compounds243. It was found that thermolysis of fraws-isomeric allyl ethers 484 or 485 at 255 °C leads to an equilibrium mixture of the two isomers in a 55 45 ratio without conversion into any other products (equation 184). Under the same conditions the isomer 487 rearranges to give the Cope-Claisen aldehyde 491 (equation 185). Presumably, the interconversion 484 485 proceeds via intermediate 486 whose structure is not favorable for Claisen rearrangement. In contrast, one of the two cyclodiene intermediates of process 487 488 (viz. 490 rather than 489) has a conformation appropriate for irreversible Claisen rearrangement243. 

A method for highly efficient asymmetric cyclopropanation with control of both relative and absolute stereochemistry uses vinyldiazomethanes and inexpensive a-hydroxy esters as chiral auxiliaries263. This method was also applied for stereoselective preparation of dihydroazulenes. A further improvement of this approach involves an enantioselective construction of seven-membered carbocycles (540) by incorporating an initial asymmetric cyclopropanation step into the tandem cyclopropanation-Cope rearrangement process using rhodium(II)-(5 )-N-[p-(tert-butyl)phenylsulfonyl]prolinate [RhjtS — TBSP)4] 539 as a chiral catalyst (equation 212)264. 

The use of a chiral auxiliary to induce stereochemical selectivity in the 3-aza -oxa-Cope rearrangement of O-aryl oximes 142 was reported by Citivello and Rapoport ... 

The allyl-transfer reaction based on 2-oxonia Cope rearrangement allows highly stereocontrolled chirality transfer. Triflic acid has been shown to induce the rearrangement of the 251 allyl sterols into 22-homoallylic sterols with high stereoselectivity without side reactions86 [Eq. (5.316)]. The protocol, however, is not effective for syn substrates (for example, 251, R = H, R = COOEt). 

Cope rearrangement (10, 31). The Pd(II)-catalyzed Cope rearrangement of chiral 1,5-dienes occurs with virtually complete 1,4-transfer of chirality.1 Example ... 

In conclusion, mention should be made of dendronised chiral salen ligands and their Co2+ and Ni2+ complexes, which were prepared for use as Jacobsen-type catalysts by diaza-Cope rearrangement [24]. However, instead of the meso compounds produced, the enantiomers will have to be synthesised directly in enantioselective manner (Fig. 4.69). 

The [3,3]-sigmatropic rearrangement of a 1,5-hexanediene is known as the Cope rearrangement and usually proceeds through a chair transition state. Generally, a large substituent at C-3 (or C-A) prefers to adopt an equatorial-like confirmation.303 304 As the reaction is concerted, chirality at C-3 (or C-4) is transferred to the new chiral center at C-l (or C-6). The reaction can be catalyzed by transition metals.305 The use of a palladium catalyst allows for the reaction to be conducted at room temperature instead of extremely high temperatures (Scheme 26. lO).306-307... 

The Claisen rearrangement, Cope rearrangement, and associated variants are powerful tools that can be used to create a number of new chiral centers in an expeditious manner, but the use of heavy metals, such as mercury, should be avoided. Of these reactions, the Ireland-Claisen ester enolate reaction provides the most versatile synthetic pathway with minimal scale up problems. 

An interesting example of the transfer of center chirality to helicity is the work by Ogawa et al., based on an asymmetric aromatic oxy-Cope rearrangement to provide nonracemic [5]helicenes (Fig. 15.8) [75]. The starting material with center chirality, bicyclo[2,2,2]ketone (-)-21 (>98% ee), was obtained by enzymatic resolution. In the annelation step, the phenanthrene derivative was subjected to aromatic oxy-Cope rearrangement, to afford a pentacyclic product in 47 % yield. The corresponding [5]helicene 22 was obtained in 7 % overall yield (> 98 % ee) after six steps. 

Y. Ogawa, M. Toyama, M. Karikomi, K. Seki, K. Haga, T. Uyehara, Synthesis of Chiral [5]Helicenes Using Aromatic Oxy-Cope Rearrangement as a Key Step, Terahedron Lett. 2003, 44, 2167-2170. 

The product is a mixture of diastereoisomers because of the chiral centre already in the molecule (ringed in green), but it is, of course, fully stereospecific for the two new black chiral centres in the four-membered ring. The next step adds vinylmagnesitim bromide to the ketone—again a mixture of diastereoisomers results. Now all the carbons in the I2-membered ring are present, and they are sorted out by the two steps that follow. The first is a Cope rearrangement a [3,3]-... 

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