Allyl ether, conformation

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. 

The different reactivity of the two n faces observed with chiral allyl ethers has been rationalized in terms of the earlier model, with the large group positioned anti inside alkoxy model) (see Section 6.2.3.1). Increased hindrance by the 0-substituent s size and restricted approach/conformational mobility may account for the increasing difference of reactivity between the two faces for cases 2, 3, and 4 (see Section 6.2.3.1). With the allylic alcohol (easel), the reversed facial preference... 

In the case of the alkenylhthium derived from the secondary (E)-y-iodo allylic ether 219, in which chelation of the metal by the alkoxy group could no longer operate, the allylzincation led after hydrolysis to 220 as a 76/24 mixture of anti and syn diastereo-mers. The stereochemical outcome was rationalized by assuming that the conformational... 

The hydrogenolysis of allylic ether and acetate (235 236, R=alkyl or COCHj) should also take place more easily when the compound can adopt a conformation in which the OR group can become parallel to the u orbital of the double bond (69). The same stereochemical requirement must also be necessary in the hydrogenolysis of a substituent in a benzylic position (70). 

Cis diastereoselectivity can be explained by using the Griesbeck rule on the possible triplet biradicals formed in the reaction. Steric interactions are minimized when the biradical assumes the optimal conformation, and this conformation accounts for the formation of the observed stereoisomer [84]. When chiral allylic alcohols were used as substrates in the reaction, cis diastereoisomers were formed. Furthermore, also in this case, a pronounced threo diastereoselectivity was observed, in agreement with a less pronounced hydroxy-directing effect when acetophenone and benzaldehyde were used [79, 84]. Chiral allyl ether gave the corresponding adduct with high diastereoselectivity [85]. 

Explain why, when the substituent Y in an allylic ether is an alkyl group, the preferred conformation is 2.106, but when it is a carbonyl or nitrile group, the preferred conformation is 2.107. 

The TMS-propargyl ether (104) rearranges to an 80 20 mixture of the ( )- and (Z)-isomers (106) and (108) in an apparent violation of this transition state proposal (equation 26). (Note that because of the stereochemical descriptor rules the sense of ( ) and (Z) is inverted by the TMS substituent.) However, replacement of the vinylic TMS grouping by hydrogen led almost exclusively to the ( )-product (109). Evidently, the normally favored transition state (E) is destabilized by steric interactions between the vinylic TMS substituent and the n-pentyl grouping (R ). The alternative conformation (F) lacks this interaction. The situation is analogous to that noted by Still in the rearrangement of lithiomethyl allyl ethers (Scheme 4). 

Cone conformations are established when 48 is converted to its tetra-allyl ether 51c, benzyl ether 5Id, or trimethylsilyl ether 51 e, when 47 is converted to its... 

The inside alkoxy effect is useful for predicting the stereoselectivity of nitrile oxide cycloaddition reactions with chiral lylic ethers. The hypothesis states that allylic ethers adopt the inside position and alkyl substituents prefer the sterically less-crowded anti conformation in transition states for these electrophilic cycloadditions . The terms inside and outside are defined in (17) for a hypothetical nitrile oxide cycloaddition transition state. Both ab initio (Gaussian 80 with 3-2IG basis set) and molecular mechanics calculations agree, each predicting the lowest-energy transition state to be the one described, i.e. (18 H outside) just above it lies one where the alkyl group is anti, OR outside and H inside (19 ). As illustrated, the former leads to a product wherein OR and the nitrile oxide oxygen are anti, the latter to one with them syn (Scheme 19). 

Fig. 4. Likely reactive conformations of alkenols bearing a remote allylic ether...

A striking preference for formation of Z-olefins is observed for the rearrangement of ethers derived from C-2-substituted allylic ethers (e.g., 8)1318-20, a protocol which provides a reliable, stercocontrolled entry to Z-trisubstituled olefins. Olefin selectivity for C-2-substituted systems has been attributed to preferential rearrangement through an RA e d conformation which relieves an eclipsing interaction between RA (the allylic substituent) and the C-2 substituent (vide supra). 

As noted previously, the [2.3] Wittig rearrangement of zirconium ester enolates demonstrates a strong preference for Z-oleftn formation. For secondary allylic ethers 16, the preferential formation of Z-i v -products suggests that rearrangement occurs through an Ra transition stale conformation in order to minimize the RA-G steric interaction62,6a. 

Examples of substrate-induced 1,2 diastereoselection have been recorded for [2,3] rearrangements of allylic ethers 12 which possess an additional allylic oxygen substituentl0-15. The observed diastereofacial selectivity is consistent with theoretical models78 which predict that stercoelectronically favored conformations for intramolecular nucleophilic addition to olefin 12 will be those for which the allylic CO cr-bond is coplanar with the 7 -system of the olefin, maximizing n-transition state. Of the two conformers which satisfy this stereoelectronic requirement, the isopropyl outside orientation, which minimizes steric interactions of the allylic substituent, predominates and is reflected in the observed diastereoselection of the rearrangement15. 

Fig. 21. Intramolecular side reactions during hydrolysis of 2-O-hydroxalkyl and 2-O-allyl ethers of glucans. Intramolecular acetal or addition product formation., favored isomer and conformation according to Lee and PerUn. l,2-0-[l,2-methyl-(5,i )-l,2-ethanediyl]-a-D-glucofuranoses and l,2-0-[l,2-methyl- 5)-l,2-ethanediyl]-a-D-glucopyranose are also formed in equilibria.

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