1 aldehyde protection dithianes, preparation

RSSiMe3 [R = Me, Et, (-CH2-)3], Zn, Et20, 0-25°, 70-95% yield. This method is satisfactory for a variety of aldehydes and ketones and is also suitable for the preparation of 1,3-dithianes. Methacrolein gives the product of Michael addition rather than the thioacetal. The less hindered of two ketones is readily protected using this methodology. ... 

Dithianes are readily prepared from aldehydes (for an overview, see 1,3-dithianes as protecting group) and offer high stability towards acids and bases. Therefore, use of the S,S-acetal unit is especially useful in multistep synthesis. A crucial step is the hydrolysis of S,S-acetals, the difficulty of which is due to the excellent nucieophilicity of sulfur. 

HS(CH2) SH, BFs-EtjO, CHjClj, 25°C, 12h, high yield, n -- l n -- 3 In cx,P-unsaturated ketones the olehn does not migrate to the P,y-position as occurs when an ethylene ketal is prepared." Aldehydes are selectively protected in the presence of ketones, except when large steric factors disfavor the aldehyde group, as in the example below. A TBDMS group is not stable to these conditions. Oxazolidines are converted to the dithiane in 70% yield under these conditions, but the use of methanesulfonic acid as a catalyst is equally effective. "... 

Initial progress was swift and the two subunits required for the CIO-C16 dithiane fragment, sulfone 12 and aldehyde 10, were easily prepared. Ester 13 was first converted to the mono-protected diol 18 by silylation followed by ester reduction (Scheme 4). The phenyl sulfone auxiliary was next installed in two steps by a Mitsunobu-like thioether formation with diphenyl disulfide and tributylphosphine followed by oxidation with Oxone . The resulting sulfone 19 was desilylated and the liberated hydroxyl group converted to an aldehyde with Swem s procedure. Subunit 12 was completed by formation of the dithiane from aldehyde 20 under standard conditions. 

In the subsequent 12 steps (Scheme 4) the two primary alcohol functions in 24 are oxidized to carboxyl functions and protected as benzyl esters. After trimethylsilyl(TMS)-pro-tection of the OH group at C4 Nicolaou then obtains the aldehyde 30. Addition of the lithium compound prepared from the dithiane 31 to the Cl side chain (Scheme 5) of 30 deli-... 

In the forward direction, diene 5 was prepared by alkylation of metallated 1,3-dithiane 9 with allylic bromide 8. In this reaction, 9 plays the role of an acyl anion equivalent . We will talk about equivalencies in more detail in Chapter 6, but at this point it is worth noticing that the dithiane will eventually emerge as the C15 protected ketone. Dienophile 4 was prepared by an aldol-dehydration reaction between nitromethane and aldehyde 10, a reaction known as the Henry reaction. The Diels-Alder reaction between 4 and... 

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