Stereoselectivity Stereospecific intramolecular

A stereospecific intramolecular imino-ene reaction was used by Weinreb and co-workers92 to provide the enantio-selective total syntheses of (-)-montanine, (-)-coccinine, and (-)-pancracine. Refluxing the imine resulting from the condensation of 151 and 152 in mesitylene produces the amine 153 (Scheme 33) as a single stereoisomer in 63% yield after removal of the silyl group from the alkyne. The high stereoselectivity is thought to arise from a concerted ene process. 

By equatorial attack on the carbonyl, a single stereoisomer is formed from tert-butylcyclohexanone. In the presence of sodium alcoholate, 84 is formed from a butadienyl-sulfonium salt with an aldehydeThe reaction is stereospecific with 85 for instance, with aldehydes the trans product is obtained.An interesting stereospecific intramolecular methylene transfer has been observed for a decalone derivative. Stereoselective epoxidation has recently been described with 79 predominantly, the trans product results. Epoxidation can be carried out in a one-pot procedure at room temperature, with MejS + Me2S04, then NaOMe formed in situ. ... 

Addition of lithium enolate (56) to trifluorocrotonate (55) proceeded smoothly in almost quantitative yields with excellent stereoselectivity. The intramolecular chelation in 57 retards the retro-aldol reaction. On the other hand, nonfluorinated crotonate (59) provided 60 in a poor yield because of the faster retro-aldol reaction [26]. The stereochemistry of the chelated intermediate (57) was proven by trapping 57 as its ketenesilylacetal (61). Pd-catalyzed Ireland-Claisen rearrangement of 61 proceeded stereospecifically to give a single stereoisomer (62), suggesting a rigid control of the three consecutive stereocenters (Scheme 3.12) [27]. 

Intramolecular nitrone cycloadditions often require higher temperatures as nitrones react more sluggishly with alkenes than do nitrile oxides and the products contain a substituent on nitrogen which may not be desirable. Conspicuously absent among various nitrones employed earlier have been NH nitrones, which are tautomers of the more stable oximes. However, Grigg et al. [58 a] and Padwa and Norman [58b] have demonstrated that under certain conditions oximes can undergo addition to electron deficient olefins as Michael acceptors, followed by cycloadditions to multiple bonds. We found that intramolecular oxime-olefin cycloaddition (lOOC) can occur thermally via an H-nitrone and lead to stereospecific introduction of two or more stereocenters. This is an excellent procedure for the stereoselective introduction of amino alcohol functionality via N-0 bond cleavage. 

In an approach to FR182877, Sorensen and co-workers generated allenoate intermediate 289 from an ce-bromo-ce,/j-unsaturated lactone and effected an intramolecular acylation to afford a-alkylidene-/3-keto-y-lactone 290 as a single stereoisomer (Scheme 19.52) [61]. Evidence for the allenoate intermediate was established by the treatment of a-bromoenoate 291 with tBuLi, which afforded the cydized compound 292 as a single stereoisomer. Treatment of the isomeric bromoenoate of compound 291 also gave 292. Hence this demonstrated a stereoselective but not stereospecific process. 

Yttrium-catalyzed cascade cyclization/hydrosilylation of 3-(3-butynyl)-l,5-hexadienes was stereospecific, and syn-19 (R =Gy, R = OGPh3) underwent cascade cyclization/hydrosilylation to form 80b (R = Gy, R = OGPh3) in 97% yield as a single diastereomer (Scheme 20). The regio- and stereoselective conversion of syn-19 to 80b was proposed to occur through an initial 5- x -intramolecular carbometallation via a chairlike transition state that resembles alkenyl olefin eomplex syn- m. followed by S-exo intramolecular carbometallation via a boatlike transition state that resembles alkyl olefin complex boat-llm. The second intramolecular carbometallation presumably occurs via a boatlike transition state to avoid the unfavorable 1,3-interaction present in the corresponding chairlike transition state (Scheme 20). 

Benzyl and allylsilanes 87 and 89 can be formed by reductive lithiation and [l,4]-retro-Brook rearrangement of benzyl and allylsulfides 86 and 88 containing silyl ethers.63 The reaction, by virtue of the intermediacy of a configurationally unstable benzyl or allyllithium, is stereoselective but not stereospecific. In the latter case, intramolecularity assures the regioselective formation of 89. 

Electrophilic substitutions of alkenyl-, aryl-, and alkynylsilanes with heteroatom-stabilized cationic carbon species generated by the action of a Lewis or Brpnsted acid (acyl cation, oxocarbenium ion, etc.) provide powerful methods for carbon-carbon bond formation. Particularly, intramolecular reactions of alkenylsilanes with oxocarbenium and iminium ions are very valuable for stereoselective construction of cyclic ether and amine units.21-23 For example, the BFj OEt -promoted reaction of (E)- and (Z)-alkenylsilanes bearing an acetal moiety in the alkenyl ligand gives 2,6-disubstituted dihydropyrans in a stereospecific manner (Scheme l).23 Arylsilanes also can be utilized for a similar cyclization.24... 

Reaction of cyclic sulfates or thionocarbonates, derived from 1,2-diols, with telluride results in stereospecific alkene formation <1995TL7209>. This is illustrated by the conversion of the cyclic sulfate OTitra-l,2-diphenyl-l,2-ethanediol 49 into fif-stilbene exclusively by Te, as shown in Equation (13). Treatment of the cyclic sulfate of 47-1,2-diphenyl-1,2-ethanediol with Te produces /ra r-stilbene exclusively. These results are accounted for by intermolecular Te Sn2 displacement followed by intramolecular Sn2 displacement to form the corresponding tellurirane. The tellurirane then thermally loses tellurium stereoselectively forming alkene. Cyclic sulfates need not be used dimethanesulfonates or di-/i-toluenesulfonates prepared from 1,2-diols also, stereospecifically, provide alkenes via telluriranes <1993CC923, 1996SL655>. 

Another frequent use of (1) and its enantiomer is the stereospecific conjugate addition of carbonyl compounds to a,p-unsaturated systems. Most published examples contain chiral imine derivatives of cyclic ketones, which add to a,p-unsaturated esters and ketones in a highly stereoselective manner (eq 13 and eq 14). When the ketone is not symmetrically substituted, reaction usually occurs at the most substituted a-position, including those cases where the ketone is a-substituted by oxygen (eq 15). High stereoselectivity can also be achieved when the Michael acceptor is other than an unsaturated ketone or ester, such as a vinyl sulfone (eq 16). Intramolecular variations of this transformation have also been described (eq 17). ... 

As mentioned previously, acyliminium ions are electrophilic enough to react intramolecularly even with nonactivated alkenic ir-systems. These cyclization reactions have been recognized and elaborated as valuable tools in the stereoselective total synthesis of quinolizidine, indolizidine and pyrrolizidine alkaloids. A typical example from Speckamp s laboratory is the highly stereospecific acid-catalyzed cyclization of (81) to (83 Scheme 40), presumably via the corresponding acyliminium ion (82). Analogously, other more complex natural products, such as the antiulcerogenically active alkaloid ma-trine (85), can be built up with high stereocontrol (Scheme 41), with an enol ether function as a more electron-rich nucleophile for the intermediate iminium ion (84). ... 

Allylic or propargylic metal compounds are often intermediates in isomerization reactions of unsaturated systems (see Section 4.5.5) the product distribution on protonation depends very much on the substitution and the conditions of hydrolysis and most often mixtures of isomers are obtained. In contrast double bond shift generally occurs on protodesilylation of allylic silanes by acids, a reaction which takes place stereospecifically anti. Only when intramolecular delivery of the proton in a chair-like transition state is possible may a different kind of stereoselectivity be effective and good 1,3- or 1,4-induction in hydrogen transfer be observed (Scheme 83). ° ... 

It was also discovered that these reactions can be conducted intramolecular-ly and that they remain stereospecific. For example, imino ene reaction of the N-sulfonyl imine derived from 246 produced two cis <5-lactones 248 and 250 as a 9 1 mixture (Scheme 44). The formation of the major (E)-product 248 can be rationalized by invoking the more favorable pericydic endo ene transition state 247. The minor (Z)-product 250 would arise from endo ene transition state 249, which suffers from A1,3 strain between the allylic methyl substituent and the cis vinyl hydrogen. Rather surprisingly, the Z -olefin isomer corresponding to 246 gave the same 9 1 mixture as did the E isomer. Based on the related loss of stereoselectivity with Z-2-butene (vide supra) it was again postulated that the... 

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