Chiral allylic ethers

Kibayashi and coworkers have used enantiometrically pure allylic silyl ethers obtained from amino acids in cycloaddition with nitrones (Eq. 8.49).71 Cyclic nitrone reacts with a chiral allyl ether to give selectively the exo and erythro isomer (de 90%). Optically active alkaloids containing a piperidine ring such as (+)-monomorine,71c (+)-coniine,71a and (-)-oncinotine71b have been prepared from the addition product. 

Enantioselective [2 + 2 cycloaddition.2 The chiral allylic ether (1), prepared from (lS,2R)-( + )-2-phenylcyclohexanol, undergoes enantioselective cycloaddition with dichloroketene to furnish, after one crystallization, optically pure (-)-2. This cyclobutanone after ring expansion and exposure to chromium(II) perchlorate gives... 

The oxygen atom has also been used to generate other functionalities, such as the aldehyde moiety in Kibayashi s syntheses of (—)-coniine (197) and its enantiomer (Scheme 1.43) (253). Here, reaction of tetrahydropyridine N-oxide 93 with a silylated chiral allyl ether dipolarophile 198 delivered the adduct 199 with the desired bridgehead stereochemistry via the inside alkoxy effect . Desilylation and hydrogenolytic N—O bond rupture with palladium(II) chloride provided the diol 200... 

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... 

Intramolecular Alkylation of Remote Double Bonds with Chiral Allylic Ethers... 

The cycloaddition of a nitrile oxide with a chiral allylic ether affords an isoxazoline with selectivity for the pre/-isomer. This selectivity increases with the size of the alkyl substituent and is insensitive to the size of the allyl oxygen substituent. However, allyl alcohols tend to form the / ar/ isomcr preferentially, although the selectivity is often low.427"434 The product of dipolar cycloadditions based on nitrile oxides, the isoxazoline moiety, can be converted into a large variety of functional groups under relatively mild conditions.3 Among other products, the addition can be used to prepare P-hydroxy ketones (Scheme 26.17).435 The isoxazoline moiety can be used to control the relative stereochemistry through chelation control.436,437... 

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]. 

Haller, J., Strassner, T., Houk, K. N. Models for Stereoselective Additions to Chiral Allylic Ethers Osmium Tetraoxide Bis-hydroxylations. J. Am. Chem. Soc. 1997, 119,8031-8034. 

The model correcdy predicts (rationalizes) the observed preference for formation of the anti rather than the syn product in the cycloaddition reactions of a wide variety of chiral allylic ethers, thus successfully laying to rest years of frustrated discussion. It also correctly predicts that as the size of R increases (Me - Ph < Et < Pr < Bu ), the preference for transition state structure (18 ) should increase leading to enhanced anti stereoselectivity (Table 15). At first, this prediction seems strange. However, once it is realized that, like the Felkin-Anh model for nucleophilic addition to a carbonyl, the outside position is actually more sterically demanding than the inside, then the prediction is sensible on purely steric grounds. Thus, the angle of approach of the nitrile oxide oxygen to the alkene actually places it nearer the outside than the inside substituent located at the allylic carbon. ... 

Asymmetric alkylations of anions of chiral allylamines 5.6 have been performed at -78°C by Ahlbrecht and Enders [1012], These reactions form 2-en-amines with high regio- and stereoselectivities. These enamines are hydrolyzed to generate 3-phenylalkanals 5.7 with a good enantioselectivity (Figure 5.4). The same types of nonracemic aldehydes 5.7 were already obtained with a similar enantioselectivity by Mukaiyama and coworkers [148] via selective alkylation of potassium anions of chiral allyl ethers 5.8 (Figure 5.4). 

Stereoselection in 1,3-dipolar cycloaddition reactions of chiral allyl ethers 01EJ01039. 

Asymmetric methoxyselenenylation. A chirally constituted Ar SeBr reagent induces asymmetric addition to double bonds. Chiral allyl ethers are accessible after oxidation and selenoxide elimination. 

The indolizidine alkaloid (+ )-monomorine I (373), isolated from Pharaoh s ant Mono-morium pharaonis, is the first example of an indolizidine alkaloid found in the animal kingdom. One enantioselective total synthesis of 373 exploits an asymmetric cycloaddition of nitrone 370 to the chiral allylic ether 369, which is prepared from 349. The conversion of 349 to a tosylate followed by treatment with -propylmagnesium bromide in the presence of... 

Slereoselection in 1,3-DC reactions of chiral allyl ethers <01EJ01033> and kinetic resolution by means of cycloaddition reaction, including 1,3-DC of nitrones <01EJO2999>, have been reviewed. 

Houk KN, Moses SR, Wu Y-D, Rondan NG, Jager V, Schohe R, Fronczek FR (1984) Stereoselective nitrile oxide cycloadditions to chiral allyl ethers and alcohols. The inside alkoxy effect. J Am Chem Soc 106 3880-3882... 

Fig. 20 Synthesis of chiral allyl ethers by reaction of a-chiral cyclic tosylhydrazones with aryl halides...

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