Dithiane coupling

An approach to the 1,3-polyol system complementary to that shown in Schemes 83 and 84 makes use of dithiane 598 as a synthetic equivalent of 603. Alkylation of the anion generated from 598 with epoxide 303 gives the coupled dithiane 599. After hydrolysis of the thioacetal, a 57 -selective reduction of ketone 600 with lithium aluminum hydride in the presence... 

Total synthesis of macrolide immunodepressants using 1,3-dithiane aldol couplings and a-bond olefin constructions 98ACR35. 

Intermediate 10 must now be molded into a form suitable for coupling with the anion derived from dithiane 9. To this end, a che-moselective reduction of the benzyl ester grouping in 10 with excess sodium borohydride in methanol takes place smoothly and provides primary alcohol 14. Treatment of 14 with methanesulfonyl chloride and triethylamine affords a primary mesylate which is subsequently converted into iodide 15 with sodium iodide in acetone. Exposure of 15 to tert-butyldimethylsilyl chloride and triethylamine accomplishes protection of the /Mactam nitrogen and leads to the formation of 8. Starting from L-aspartic acid (12), the overall yield of 8 is approximately 50%, and it is noteworthy that this reaction sequence can be performed on a molar scale. 

Scheme 8.31 Smith Ill s three- and multicomponent linchpin coupling of metalated silyl dithiane 109 with epoxides.

The multicomponent linchpin coupling of silyl dithianes with epoxides was very efficiently used to access both the AB and CD spiroketal fragments of spongistatin. 

The described procedure has been widely used by Smith III and coworkers [250] in the efficient total synthesis of natural products containing extended 1,3-hydroxylated chains. This architecture is often found as a structural element in polyene macrolide antibiotics [251] such as mycotoxin A and B, dermostatin, and roxaticin. The Smith group used the above-mentioned approach (e. g., as five-component coupling) for the synthesis of the pseudo-C2-symmetric trisacetonide (+)-2-471 [252], which was employed by Schreiber and coworkers [253] within the synthesis of (+)-mycotoxin A (2-470a) (Scheme 2.108). Thus, lithiation of 2.5 equiv. dithiane 2-462b followed by treat-... 

The formation of S-oxides has also been observed when oxidizing a variety of 5-substituted 2-tert-butyl-l,3-dithianes in wet acetonitrile. In an undivided cell, 4-substituted 1,2-dithiolane-l-oxides were oblained (Scheme 25) [113]. A coupled cathodic process, in this case, was the reduction of protons formed in the anodic reaction. 

Assembling a five-component coupling product in a single operation further extended this methodology. Following alkylation of dithiane 78 with epoxide (—)79 (2.6 equivalent each) to generate the unrearranged alkoxy dithiane 80, sequential addition of HMPA and (—)-epichlorohydrin 81 (1 equivalent) furnished the bis(silyloxy dithiane) carbinols (- -)82 in 66% yield (equation 29) . ... 

Also the preparation of methyltriphenylphosphonium dichromate ((Ph3PMe)2Cr207) and the application of this compound as efficient, inexpensive, stable and mild reagent for coupling a variety of aliphatic and aromatic thiols and aliphatic dithiols to their corresponding acyclic and cyclic disulfides has been published <2006JSF441> 1,2-dithiane was obtained by this procedure in 90% yield. 

Ab initio calculations at the MP2 level of theory of a collection of substituted 1,3-dioxanes, 1,3-oxathianes, and 1,3-dithianes have been employed to study both the position of the conformational equilibria and the validity of the Perlin effect <2005T7349>. The 7h,c coupling constant proved to be a valuable tool in conformational analysis both twist conformers, in addition to the chair and alternative chair forms, could be readily identified simply by comparing experimental Vh,c coupling constants to the corresponding calculated values in the particular forms. In addition, the Perlin and reversed-Perlin effects of the C2-H fragments, c in 1,3-dioxanes,... 

Another study from low-temperature E NMR spectra showed that the inversion of octafluoro-l,4-dithiane has A// = 8.2 kcal mop , AG (25°C) = 10.7kcalmoU and = —8.4e.u. The geminal coupling, is 231Hz... 

Dithioacetals (see also dithianes and dithiolanes) alkylation of 98 as acyl anion equivalents 75 carbanions of 87,97-102 cleavage of 14-18,98,102 desulfurization of 78 metal-catalysed coupling 127 reaction with Grignard reagents 127 reductive lithiation of 89 synthesis of 12-19,97-102 Dithioacids synthesis of 40... 

Sunay, U. Fraser-Reid, B. Synthetic studies relating to the C1-C9 eastern" half of rosara-micin. Tetrahedron Lett. 1986, 27, 5335-5338. Smith, A. B. Pitram, S. M. Boldi, A. M. Gaunt, M. J. Sfouggatakis, C. Moser, W. H. Multicomponent linchpin couplings. Reaction of dithiane anions with terminal epoxides, epichlorohydrin, and vinyl epoxides efficient, rapid, and stereocontrolled assembly of advanced fragments for complex molecule synthesis./. Am. Chem. Soc. 2003, 125, 14435— 14445. 

Five steps were required to convert 75 into the iodide coupling partner 44 needed for union with dithiane 43 (Scheme 17.16). Thioacetal formation31 and concomitant deketalisation were instigated by reacting 75 with 1,3-propanedithiol under Lewis acid conditions. Triol 76 was isolated in 65% yield. The less-hindered primary hydroxyl of 76 was then selectively 0-tosylated, and the remaining hydroxyls masked as tert-butyldimethyl silyl (TBDMS) ethers. Iodide displacement on 77 with sodium iodide and copper bronze,32 and transketalisation with N-chlorosuccinimide (NCS)/silver nitrate33 finally secured 44. 

Let us turn now to the other coupling partner, aldehyde 58 it was synthesised by the pathway shown in Scheme 17.18. The first step was a Sharpless catalytic asymmetric epoxidation on ( )-crotyl alcohol with the oxidant derived from (—)-diethyl tartrate. An in situ derivatisation with r-butyldiphenylsilylchloride was then performed. The desired epoxide 59 was readily isolated in 76% overall yield after chromatography. Treatment of 59 with 2-lithio-l,3-dithiane in THF and 1,3-dimethyl-3,4,5,6-tetrahydro-2(l/7)-pyrimidinone (DMPU also known as N,N-... 

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