Tetrahydropyrans polysubstituted

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... 

Scheme 1.14. Domino ene/Sakurai reaction for the synthesis of polysubstituted tetrahydropyrans.

A three-component domino process consisting of an ene reaction followed by the addition of an allylsilane to afford polysubstituted tetrahydropyrans in generally good yield was described by Marko and coworkers [115]. However, the nature of the products formed in this process depends heavily on the Lewis acid employed as a catalyst. Thus, reaction of the allylsilane 4-333 with an aldehyde in the presence of BF3-Et20 led to the domino products 4-334, whereas in the presence ofTiCL the diol 4-332, and in the presence of Et2AlCl the alcohol 4-335, were obtained (Scheme 4.74). The latter compound can then be transformed in stepwise manner to 4-334, using the same aldehyde as previously. However, it is also possible to use another aldehyde to prepare tetrahydropyrans of type 4-336. 

The tetrahydropyran-based iron complex 524 can undergo demetallation followed by a cycloaddition reaction with ethyl propiolate to afford a regioisomeric mixture of polysubstituted chromans (Scheme 116) <2001TL6987>. 

Aldehydes, ketones, and acetals react with allyltrimethylsilane in the presence of a catalytic amount of BiX3 (X = C1, Br, OTf) to give homoallyl alcohols or homoallyl alkyl ethers (Equation (52)).91-93 The BiX3-catalyzed allylation of aldehydes and sequential intramolecular etherification of the resulting homoallylic silyl ethers are involved in the stereoselective synthesis of polysubstituted tetrahydropyrans (Equation (53)).94,95 Similarly, these Lewis acids catalyze the cyanation of aldehydes and ketones with cyanotrimethylsilane. When a chiral bismuth(m) catalyst is used in the cyanation, cyanohydrines are obtained in up to 72% ee (Equation (54)). a-Aminonitriles are prepared directly from aldehydes, amines, and cyanotrimethysilane by the BiCl3-catalyzed Strecker-type reaction. 

Dihydropyrans represent an attractive and challenging class of compounds as many of them are key intermediates for the synthesis of several natural products [171]. In particular, their olefin function has great S3mthetic value for the further functionalization to obtain polysubstituted tetrahydropyrans [172] that constitute... 

The allylation and cyanation of aldehydes and ketones are mediated by BiCl3 and BiBr3 [174, 175]. When a chiral bismuth(lll) catalyst is used for cyanation, cyanohydrins are obtained in up to 72% ee (Scheme 14.85) [175]. The Bi(OTf)3-promoted intramolecular Sakurai cyclization of homoallylic alcohols is involved as a key step in the stereoselective synthesis of polysubstituted tetrahydropyrans (Scheme 14.86) [176]. In the presence of the BiCl3-xMl binary catalyst, allyltrimethylsilane [177] and silyl enolates [178] are acylated to give aUyl ketones and /l-dikelories, respectively. 

The one-pot diphenylproHnol silyl ether 1 catalyzed Michael reaction of cro-tonaldehyde and nitroalkene arrives at the intermediate 247, which is followed by the an aza-Henry reaction/hemiaminalization process to a proposed alcohol intermediate, followed by Lewis acid-mediated allylation or cyanation (Scheme 7.54). A later report of polysubstituted piperidine 251 preparation was carried out through a Michael addition of 249 and 250 and an aminahzation reaction process, remarkably in water [123]. This process was also carried out to form tetrahydropyrans... 

In particular, it is still a challenge to devise methods which allow to generate polysubstituted tetrahydropyrans and piperidines with a predefined stereochemical arrangement of the substituents. The strive for efficiency in synthesis demands, that those steps that lead to the closure or formation of the heterocyclic ring should at the same time generate the largest possible number... 

The same strategy has been applied in the cascade, where enone (471) afforded the polysubstituted tetrahydropyran derivatives (472) (R = R CH=CH). ... 

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