Protecting groups dithianes

M (marginal) indicates that the stability of the protected functionality is marginal, and depends on the exact parameters of the reaction. The protective group may be stable, may be cleaved slowly, or may be unstable to the conditions. Relative rates are always important, as illustrated in the following example (in which a monothioacetal is cleaved in the presence of a dithiane), and may have to be determined experimentally. 

Similarly, in another example, alkylation of 111 with diepoxide (—)-115 (1 equiv.) in the presence of HMPA (1.3 equiv.) furnished diol (+)-117. Protection of (+)-117 to form the acetonide, removal of the silyl protecting groups (TBAF), and hydrolysis of the dithiane with Hg(Cl04)2 provided the diketone (+)-118. Hydroxy-directed syn-reduction of both carbonyl groups with NaBI U in the presence of Et2BOMe, and triacetonide formation, followed by hydrogenolysis and monosilylation, afforded the desired Schreiber subtarget (+)-119, which was employed in the synthesis of (+)-mycoticins A and B (Scheme 8.31) [56b]. 

Direct oxidation of A9-THC at position C-11 involves mainly an isomerization to A8-THC another opportimity in the synthesis of A9-THC-metabolites is the pretreatment of terpenoid synthons by introduction of protective groups, e.g., 1,3-dithiane (6.1 in Fig. 6) followed by the condensation with olivetol (6.2) [76]. The formed product is a protected derivate... 

An effective and mild electrocatalytic procedure for the deprotection of the 1,3-dithiane group of (68), giving the ketone (67), has been developed by using a small amount of tris(/ -tolyl)amine as a homogeneous electron-transfer catalyst (Scheme 26) [86]. The scope and limitations are discussed in detail [87]. The method can be applied also for oxidative removal of the 4-methoxybenzyl thioether protecting group from poly-cystinyl peptides [88]. 

Dithioketals, especially the cyclic dithiolanes and dithianes, are also useful carbonyl-protecting groups. These can be formed from the corresponding dithiols by Lewis acid-catalyzed reactions. The catalysts that are used include BF3, Mg(03SCF3)2, Zn(03SCF3)2, and LaCl3.100 S-Trimethylsilyl ethers of thiols and dithiols also react with ketones to form dithioketals.101... 

Danishefsky s total synthesis of 317 and its chlorine free precursor monocillin I 316 features an RCM reaction with a substrate 310 that in addition to a dithiane protective group contains a vinyl epoxide and a diene moiety at... 

The reaction of aldehydes or ketones with ethane-1,2-dithiol or propane-1,3-dithiol to form 1,3-dithiolanes or 1,3-dithianes is an important reaction, as these compounds under suitable conditions are acyl anion equivalents (see Section 5.9, p. 626). These cyclic dithioacetals have been less used as protective groups, though when required are formed in high yield in the presence of boron trifluoride-etherate.138... 

Oxathiolanes (11) are formed from aldehydes and ketones by reaction with 2-mercaptoethanol (HS-CH2-CH2OH) in the presence of, for example, zinc chloride-sodium acetate in dioxane solution at room temperature,139 or boron trifluoride-etherate.140 They are more stable to an acidic medium than the 1,3-dithianes, and therefore may be the protective group of choice in certain instances. 

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. 

Thermolysis of 3-(ort o-anisoyl)-l-(l-piperidinyl)-3-cyclobutenes 807 in the presence of mesitylene affords angular-fused xanthones 809 via formation and ring closure of the intermediate 808 (Scheme 226) <1997TL3663>. Linear-fused xanthones 810 are prepared by nucleophilic addition of aryl and heteroaryl lithiates to dithiane protected benzopyrone-fused cyclobutenediones 811 followed by hydroysis of the dithiane protecting group (Scheme 227) <1996JA12473>. 

McHale, W.A. and Kutateladze, A.G. (1998) An efficient photo-SET-induced cleavage of dithiane-carbonyl adducts and its relevance to the development of photoremovable protecting groups for ketones and aldehydes. Journal of Organic Chemistry, 63, 9924—9931. 

RCeCl2. The reagents, prepared in situ from RLi + CeCK, are more reactive than RLi in 1,2-addition to carbonyl groups. An example is the reaction with 2-alkoxypropionoyl-l,3-dithianes (1), prepared from methyl (S)-lactate.2 The dias-tereoselectivity obtains even when the protecting group is incapable of chelation. 

The location of the silyl protecting group in the coupling product from the reaction between a silyl dithiane and two different chiral epoxides is controlled by the order of the addition of the epoxides. Subsequent cyclisation of the derived 1,3-diketones provides an efficient route to a variety of 2,6-disubstituted dihydropyran-4-ones 39 <07JOC4280>. 

The next carbonyl protecting group stems from an attempt to retain the carba-nion-stabilising properties of the dithiane 45-acetal whilst increasing its hydro-... 

Scheme 16.11 shows the completion of the total synthesis of azaspiracid-1, which followed with slight modifications, the synthesis of the originally proposed structure of azaspiracid-1 (la). This chemistry was also carried out with the corresponding ABCD enantiomer in similar yields. Thns, lithiation of dithiane 51 (n-BuLi n-BnjMg) followed by addition into pentafluorophenol ester 68 resulted in CJ-C27 ketone 69 (50% yield). Ketone 69 was then elaborated into diacetate 70, this time as the TBS ether at C-25, as this protecting group was easier to remove than the acetate used in the earlier work directed toward the original stractnre (see Scheme 16.8). Stille coupling of this allylic acetate (70) then proceeded smoothly, as before, affording the complete Cj-C q backbone 71, which was successfully elaborated to the correct structure of azaspiracid-1 (1), identical in all measured physical properties ( H NMR, C NMR, Rf, [aj ) to the natural material.

The reaction usually occurs at the less substituted carbon of the oxirane ring (Scheme 62 and Scheme 67) 293,297 However regioisomeric dithianyl alcohols are obtained from 2-lithio-1,3-dithianes and the protected 3, y-epoxy alcohols shown in Scheme 66 (entry b). The observed regioselectivity is very different when methoxymethyl or benzyl protecting groups are used. This has been explained by the different... 

---