Pyrans diastereoselective synthesis

Diastereoselective Synthesis of 2,6-Disubstituted Tetrahydro-2F/-pyrans via Oxypalladation... 

The reaction of 6-ethylthio-3,4-dihydro-2-methoxy-27f-pyran with aldehydes is promoted by SnCU, and has been used in the diastereoselective synthesis of highly functionalized tetrahydropyrans (Eq. 53) [88a] whereas the reaction of 2,2-diethoxy-6-(ethylthio)-3,4-dihydro-2//-pyran with aldehydes in the presence of SnCU gives aldol adducts of glutarates (Eq. 54) [88b]. 

The HDA reaction features in a diastereoselective synthesis of c/j-2,6-disubstituted 5,6-dihydro-2//-pyrans, but this is based on the initial formation of a dihydropyran-4-one. Regio- and stereo- chemistry are controlled during the reduction to the pyranol and an ester enolate Claisen rearrangement completes the sequence <97AJC43>. 

Carbopalladation has also been employed in the construction of six-membered rings. Most examples are 6-exo cyclizations as is the pyran ring synthesis (107—>108) used in the construction of ( )-6a-epipretazettine 109 and ( )-tazettine (Scheme 17). The Heck cyclization formed a quaternary center with a diastereoselectivity in excess of 20 1. The selectivity of the reaction is of particular interest in this case as it provides information about the orientation of the carbon-palladium a bond and the reacting aUcene in the carbopalladation transition state. Two limiting transition state geometries for the closure are intermediate 110, which leads to the observed product, and intermediate 111, which would lead to a diastereomer. In the preferred transition state 110, the carbon-palladium (7 bond and alkene are eclipsed, which is a lower energy state than the corresponding twisted orientation 111. 

An efficient and diastereoselective synthesis of 5,6-dihydro-2H-pyran-2-acetates involves a Prins cyclization of acrylyl enol ethers mediated by TMSOTf.This strategy was used in the total synthesis of the natural compound (+)-civet (13JOC12182). Highly functionalized tricyclic dihydropy-ranopyrrolidin-2-ones are formed by a catalytic P,Y-selective Diels-Alder [4 + 2] annulation of a,P-unsaturated y-butyrolactams, in good yields and enantioselectivities (Scheme 8) (13AGE11329). 

Ene JJ, Yong RL, Ha-Jin L (2009) Iodine-catalyzed one-pot synthesis of 27/pyrans by domino knoevenagel/67i-electrocylization. Bull Korean Chem Soc 30 2833-2836 Sabitha G, Bhikshapathi M, Nayak S, Yadav JS (2011) Molecular iodine-catalyzed, one-poL diastereoselective synthesis of4-amido tetrahydropyrans. Synth Commun 41 8-15 Mallik AK, Mandal TK, Pal R, Patra A (2011) Trans-2-Phenyl-4-thiophenoxy-3,4-di-hydro-2H-l-benzothiopyran. Molbank 2011 M719... 

Fig. 63 Porco s synthesis of pyranic azaphilone scaffolds and Franck s diastereoselective synthesis of the epicocconone-related dihydropyranic azaphilone core...

Sagar, R., Park, J., Koh, M., Park, S. B. (2009). Diastereoselective synthesis of polycyclic acetal-fused pyrano[3,2-c]pyran-5(2//)-one derivatives. Journal of Organic Chemistry, 74, 2171-2174. 

J. Pandey, N. Anand, R.P. Tripathi, L-Proline catalyzed multicomponent reaction of 3,4 dihydro-(2H)-pyran, urea/thiourea, and aldehydes diastereoselective synthesis of hexahydropyranopyrimidinones (thiones). Tetrahedron 65 (2009) 9350-9356. 

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

Ring-closing reactions promoted by mercuric salts are valuable transformations which find an increasing use in the total synthesis of various natural products.130-140 Several examples of solvomercurations demonstrating the applicability of these transformations to the synthesis of natural product precursors are presented in Table 2. Piperidines (entry a), 141 pyrans (entries b-d), 142-144 and furans (entries e, f)14S>146 have been obtained in good yields and diastereoselectivity. These derivatives serve as starting materials for various natural products and can be demercu-rated under reducing conditions.147... 

The successful implementation of this strategy is shown in Scheme 1.370. The optically pure stannane 1441 was transmetalated in situ with 1442, preparing a borane reagent that condensed with 1440. After methylation, 1443 was isolated in excellent yield with 10.5 1 diastereoselection. At this point, 1443 was elaborated to incoprorate the pyran moiety (five steps), and the side chain was converted to an aldehyde (two steps). Overall, this reaction sequence to 1444 was accomplished in 46% yield. The skipped triene fragment was then incorporated via the anion of sidfone 1445. Saponification of the pivalate ester then completed the synthesis of 1191a. 

In particular, the key intermediate product 381 in the synthesis of wighteone was prepared by the oxidative rearrangement of 3 -iodotetraalkoxychalcone 380 [474] and the key step in the synthesis of ( )-indatraline involved the HTIB-promoted diastereoselective ring contraction of a 1,2-dihydronaphthalene 382 to construct the indane ring system 383 (Scheme 3.152) [475]. A similar oxidative rearrangement of 3-cinnamoyl-4-hydroxy-6-methyl-2/7-pyran-2-ones with HTIB in dichloromethane followed by cycliza-tion was used by Prakash and coworkers for the direct conversion of o-hydroxychalcones into isoflavone derivatives [476]. 

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