Secondary allylic ethers

The aliphatic Claisen rearrangement of secondary allyhc ethers has been recognized to provide E double bonds (Eq. 3.1.20) [28, 29]. The Claisen rearrangement of C4 and C5 substituted vinyl ether provided a 90 10 ratio of ( )- to (Z)-unsaturated aldehydes (Table 3.1.1, entry 1). An increase in the steric bulk of the C5 substituent produced higher stereoselectivity (entry 3). 

These results indicated that the E/Z isomer ratios in the Claisen rearrangements corresponded to the free-energy change for the conversion of a substituent from the equatorial to the axial position of a cyclohexane. Furthermore, using the well-established chair model for the transition state (Eq. 3.1.21), Faulkner has expected that the axial substituent r would introduce a relatively large 1,3-diaxial interaction with substituent and thus increase the stereoselectivity of the Qai-sen rearrangement [27]. 

With this manner, the Claisen rearrangement of vinyl ethers of secondary aUyUc alcohols provides E-olefinic aldehyde and takes advantage of E-selectivity for total synthesis of many natural products. 

The synthesis of the C1-C13 fragment of amphrdinoUde B, which is a 26-mem-bered macrolide, is proceeded via Claisen rearrangement of the ether as a key step in an expected procedure, leading to the aldehyde in excellent yield (Eq. 3.1.22) 

The optically active (20i )-de-AB-cholesta-8(14),22-dien-9-one (19) and (20S)-de-AB-isocholesta-8(14),22-dien-9-one (20), which are synthetic precursors for metabolites of vitamin D, were prepared by Suzuki and Kametani s group [31]. The Claisen rearrangement provided the separable aldehydes 17 and 18 (Eq. 3.1.23). Following decarbonylation of 17 with (PhsPlsRhCl produced 19 and the same treatment of the C20 epimer 18 gave 20. 

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DDQ, wet CH2CI2, 70—92% yield. Anomeric and secondary allylic ethers could not be cleaved under these conditions. ... 

Copper(I) salts of enamines have been allylated with the 2-allyloxybenzimidazoles to give y,5-unsaturated ketones upon hydrolysis (79CL957). Primary allylic ethers react preferentially at their a-carbon with retention of double bond configuration whereas secondary allylic ethers react mainly at the y-carbon to afford alkenes of predominantly (E)-stereochemistry. 

Recent methods for the cleavage of allyl ethers that have that have yet to be tested on the anvil of complex target synthesis include (a) diborane generated in situ by reaction of sodium borohydride with iodine in THF at 0 °C (cyanoT ester, nitro, acetonide and tetrahydropyranyl groups survive) 434 (b) cerium(Ill) chloride and sodium iodide in refluxing acetonitrile (benzyl. THP and Boc groups survive) 435 (c) iodotrimethylsilane in acetonitrile at room temperature 436 and (d) DDO in wet dichloromethane (secondary allyl ethers, benzyl, acetate and TBS groups survive).437... 

Scheme 7-95 Allylzincation of metallated secondary allylic ethers, amines and thioethers.

Studies on the nonracemic methylenecyclododecyl ethers (164 equation 37) led to similar conclusions. With HMPA as a cosolvent the secondary allylic ether (164a) afforded mainly (86 14) the ( )-homoallylic alcohol (165a) of 95% ee. The tertiary ether (164b) yielded a 98 2 ( ) (Z) mixture, but the major product (165b) was 40% racemic. A dissociative rearrangement process could account for this result. Without HMPA both ethers rearranged in poor yield (5-30%) to nearly 1 1 mixtures of ( )- and (Z)-cycloalkenes. 

These results are consistent with the chelated transition states depicted in Scheme 18. Steric interactions between the substituent and the carboxamide favor (AC) for ( )-allylic ethers. The R -substi-tuent of a (Z)-allylic ether, though less affected by this interaction, still experiences a certain degree of steric strain in the anti transition state (AB) thus diminishing anti selectivity. Enantioselectivity is controlled by the substituents R and R on the pyrrolidine ring. As pictured in Scheme 18, bonding occurs preferentially on the face of the enolate anti to R. For the diastereomeric secondary allylic ethers (Table 21, entries 8) transition state (AB) represents the matched arrangement for R = H and R = alkyl, whereas (AC) is matched for R = alkyl and R = H. The former arrangement would lead to an ( )-pro-duct and the latter to a (Z)-product. 

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. 

Organo-copper Reagents.—The heterocuprate (29) reacts with the readily synthesized secondary allylic ether of 2-hydroxybenzothiazole (28) to give the substitution product (30) with almost complete regioselectivity and in high yield (75%). The E Z ratio in compound (30) is strongly influenced by temperature. 

The air-stable complex [Ir(cyclo-octadiene)(PMePh2)2]PF6, after activation with hydrogen, isomerizes allyl ethers to the corresponding frans-propenyl ethers at room temperature with very high stereoselectivity ( 97%) and in high yield (3=95%) [equation (6)]. This appears to be the first stereoselective conversion of alkyl ethers into rrans-propenyl ethers, but the reaction is limited to primary allyl ethers, secondary allyl ethers being unaffected even at 65 °C. 

The use of secondary allylic ether in the Perrier rearrangement has not been precedented most likely because of its poor leaving group ability. Typically, allylic acetate, mesylate, or tosylate are employed as the functionality for activation. 

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