Stereocontrol homoallylic

Evans described another demonstration of homoallylic stereocontrol (1,3-asymmetric induction) in the hydroboration of 72 (dr =91 9, Scheme 7.13) [29]. It is important to note, however, that these studies clearly underscore the fact that the diastereoselectivity of the process is dictated by subtle con-... 

Recently, a new multicomponent condensation strategy for the stereocontrolled synthesis of polysubstituted tetrahydropyran derivatives was re-published by the Marko group, employing an ene reaction combined with an intramolecular Sakurai cyclization (IMSC) (Scheme 1.14) [14]. The initial step is an Et2AlCl-promoted ene reaction between allylsilane 1-50 and an aldehyde to afford the (Z)-homoallylic alcohol 1-51, with good control of the geometry of the double bond. Subsequent Lewis acid-media ted condensation of 1-51 with another equivalent of an aldehyde provided the polysubstituted exo-methylene tetrahydropyran 1-53 stereoselectively and... 

The opening of cyclopropylcarbinols to homoallylic bromides constituted the first use of cyclopropyl compounds for the stereocontrolled synthesis of natural products. The cyclopropyl conjunctive reagents enhance the richness of this notion. The stereocontrolled opening of vinylcyclopropanes by a homopentadienyl proton shift provides an approach to trisubstituted olefins and thereby a new strategy. The fungal prohormone methyl trisporate B (224) as summarized in Scheme 15 illustrates this conceptual development97). 

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). 

The same allyl-metallation protocol can be used for the preparation of allylstan-nane 191. Taking advantage of the greater nucleophilic propensity of the allylstan-nane function over the allylsilane one, 191 was treated with various aldehydes in the presence of Et20BF3, affording the homoallylic alcohols 192 in excellent yields (Scheme 13.67) [86]. It is noteworthy that complete syn-stereocontrol is observed in all these transformations. 

The homoallylic alcohols 192, 194 and 195 can be easily transformed into the corresponding exo-methylene tetrahydropyrans 189 and 196 by a Bi(III)-promoted IMSC condensation (Scheme 13.69). Tetrahydropyrans 189 and 196 are obtained in excellent yields and with complete stereocontrol. 

A stereocontrolled synthesis of 2,4,5-trisubstituted tetrahydropyrans 331 can be achieved via a Lewis-acid-catalyzed intramolecular Prins cyclization of homoallylic acetals 332. Incorporation of a variety of substituents at C-4 of the resulting tetrahydropyrans is possible by simple variation of the reaction conditions (Equation 141, Table 13) <2001CC835>. 

In order to prevent competing homoallylic asymmetric epoxidation (AE, which, it will be recalled, preferentially delivers the opposite enantiomer to that of the allylic alcohol AE), the primary alcohol in 12 was selectively blocked as a thexyldimethylsilyl ether. Conventional Sharpless AE7 with the oxidant derived from (—)-diethyl tartrate, titanium tetraisopropoxide, and f-butyl hydroperoxide next furnished the anticipated a, [3-epoxy alcohol 13 with excellent stereocontrol (for a more detailed discussion of the Sharpless AE see section 8.4). Selective O-desilylation was then effected with HF-triethylamine complex. The resulting diol was protected as a base-stable O-isopropylidene acetal using 2-methoxypropene and a catalytic quantity of p-toluenesulfonic acid in dimethylformamide (DMF). Note how this blocking protocol was fully compatible with the acid-labile epoxide. 

Cahiez, Knochel, and co-workers have developed a mixed catalytic system consisting of MnBr2/GuGl and diethyl-zinc in iV,A -dimethylpropyleneurea (DMPU), which can be used for the stereocontrolled formation of tetrahydro-furan organozinc compounds from readily available unsaturated bromoacetals. The organozinc compounds are readily transmetalated with GuGN-2LiGl, and upon treatment with ethyl (o -bromomethyl)acrylate or ethyl propiolate homoallyl- and allyl-substituted bicyclic tetrahydrofurans are obtained in 71% and 63% yield (Scheme 70). 

Stereocontrolled epoxidation of acyclic systems. Stereoselectivity in the epoxi-dation of homoallylic alcohols is usually low. Nonetheless Kishi etal. have observed... 

By analogy to the halolactonization reaction, the synthesis of cyclic iodocarbonates has been studied with the aim of functionalizing a double bond under regio- and stereocontrol, starting from allylic or homoallylic alcohols. These heterocyclic intermediates are employed for the synthesis of epoxy alcohols, diols and triols. 

Starting from allylic and homoallylic amines7-8, iodocyclocarbamation occurs with high stereocontrol and 1,2-asymmetric induction only if bulky groups are involved. Thus. 3-/er/-butoxy-carbonylamino-4-phenyl-l-butene (1, R = H), readily obtained from ethyl (R)-A -Boc-phenyl-alanate, cyclizes upon treatment with 3 equivalents of iodine in dichloromethanc to afford a mixture of trans- and cw-4-benzyl-5-iodomethyl-2-oxazolidinone (2) in a 60 40 ratio. Better results are obtained when a bulky group, such as an iY-benzyl group, is introduced. 

A convergent, stereocontrolled total synthesis of the microtubule-stabilizing macrolides, epothilones A and B was achieved in the iaboratory of S.J. Danishefsky. During their investigations, they examined several approaches to construct these natural products. One possible strategy to introduce the Cl 5-hydroxyl group in an enantioselective fashion was to use Keck s asymmetric allylation method. Under standard conditions, the reaction provided the desired homoallylic alcohol in good yield and excellent enantioselectivity. 

The use of allyltins and y-substituted allyltins in the stereocontrolled synthesis of homoallylic alcohols. ... 

A related reaction is the [2,3] Wittig rearrangement.33,37 This goes via a live-membered transition state - we shall not go into any more detail about that - but it too is a useful reaction both for making homoallylic alcohols and because of the stereocontrol that can be achieved in the process. Allylic ether 150 gives38 only the diastereoisomer shown of alcohol 152. The [2,3]-sigmatropic rearrangement 151 creates an -alkenc at the expense of a Z-alkene and two new chiral centres at the expense of one. The immediate product of the [2,3]-shift is an oxyanion instead of a carbanion. 

The influence of adjacent stereogenic centers on the diastereoselectivity of the cyclization is addressed in entries 4 13. Alkyl or aryl substituents in the homoallylic position lead only to a moderate preference for the 4,6-m-product (Table 14, entries 4 7)9. Surprisingly, the triflu-oromethyl group exerts complete stereocontrol, which is attributed to its steric and additional electronic repulsion of the enolate moiety in the cyclization transition state (for a detailed discussion see the preceding section). The intramolecular reactions of the bissulfone derivatives (Table 14, entries 11 -14)19 feature a contrathermodynamic production of mainly civ-substituted vinylcyclopentanes. Epimerization of the zr-allyl complex is faster than cyclization, so that an equilibrium between the different isomeric zwitterions is established. Due to unfavorable steric interactions with the substituent R, palladium is preferentially located irunx to R in the cyclization transition state favoring the m-product. The use of toluene, tetrahydrofuran, and acetonitrile as solvents results in poorer diastereoselectivities. Some restrictions apply to the kind of nucleophile employed, thus 2-oxo esters may only give the 0-alkylated product (cf. Table 12)2 19-20. 

In 1977, Bartlett and Jemstedt (17) developed a stereocontrolled synthesis of 1,3-diols from homoallylic alcohols (Scheme 7). They found that diethyl 4-penten-2-yl phosphate 65 undergoes an intramolecular cyclisation in the presence of iodine to set up both groups in the ring 66 cis and presumably diequatorial. Arbuzov reaction then gives the cyclic phosphate 67 more than 90% diastereochemically pure. 

Cyclizations. A stereocontrolled synthesis of trisubstituted tetrahydropyrans by condensation of homoallylic alcohols with aldehydes is developed. Treatment of THP ethers derived from unsaturated alcohols with triflic acid leads to oxygen heterocycles. ... 

Koreeda and Hamann have reported the use of silyl tethers in stereocontrolled syntheses of branched-chain 1,4-diols and 1,5-diols [61]. Exposure of (bromomethyl)silyl ethers prepared from the corresponding homoallylic alcohols with Bu SnH in the presence of AIBN allowed smooth conversion to the corresponding cyclic siloxanes, from which diol products were obtained using standard, oxidative cleavage protocols. While monosubstituted olefin 149 selectively underwent 1-endo cyclization, di- and trisubsti-tuted olefins 150 and 151 preferentially reacted through the 6-exo mode with complete stereocontrol, affording the diol products 152 and 153, respectively (Scheme 10-50). 

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