1.3- Dithianes aldehydes

The 1,3-dithiane-2-ethanol (2.343) was readily prepared in a three-step elaboration (Scheme 2.71). The coupling of 1,3-dithiane and bromoacetaldehyde diethyl acetal afforded acetal 2.342. Treatment of the resulting 2.342 with p-toluenesul-fonic acid generated the dithiane aldehyde and subsequent reduction by NaBH4 furnished alcohol 2.343 in 63 % over two steps. 

Synthesis of dienyl chloride 2.349, the dithiane coupling partner for dithiane aldehyde 2.338, was accomplished in five steps from commercially available cis-2-butene-l,4-diol (Scheme 2.72). To this end, monosilylation of 2.344 as the TBS ether and this allyl alcohol was then oxidized with accompanying Zto E isomerization by PCC [122] to afford the enal 2.346 in 73 % yield. a,]S-unsaturated ester 2.347 was accessed by the Still—Gennari modification [219] of the Homer-Wads worth-Emmons olefination in good yield and selectivity (92 %, Z/E — 16 1). Reduction of the resulting ester 2.347 to produce allyl alcohol 2.348, in turn was chlorinated by treatment with LiCl and methanesulfonyl chloride to furnish the requisite dienyl chloride 2.349. 

After the umpolung of an aldehyde group by conversion to a l,3 dithian-2-ide anion (p. 17) it can be combined with a carbonyl group (D. Seebach, 1969, 1979 B.-T. GrO-bel, 1977 B). Analogous reagents are tosylmethyl isocyanide (TosMIC), which can be applied in the nucleophilic formylation of ketones (O.H. Oldenziel, 1974), and dichloromethyl lithium (G. KObrich, 1969 P. Blumbergs, 1972 H. Taguchi, 1973),... 

A new class of synthetic aldehyde reactions involves effectively reversing the polarity of the carbonyl group by forming a dithiane intermediate. 

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. ... 

Dimethyl-2-sila-l,3-dithiane, BF3 Et20, CH2CI2, 0°, 82-99% yield. This method was reported to be superior to the conventional synthesis because cleaner products are formed. Aldehydes are selectively protected in the presence of ketones, which do not react competitively with this reagent. 

DDQ, CH3CN, H2O (9 1), 0.5-6 h, 30-88% yield. Dithiane derivatives of aromatic aldehydes give thioesters in low yields dithiolanes are not effectively cleaved. 

The (V-methyldihydrodithiazine 125 has also been used as an effective formyl anion equivalent for reaction with alkyl halides, aldehydes, and ketones (77JOC393). In this case there is exclusive alkylation between the two sulfur atoms, and hydrolysis to give the aldehyde products is considerably easier than for dithianes. However, attempts to achieve a second alkylation at C2 were unsuccessful, thus ruling out the use of this system as an acyl anion equivalent for synthesis of ketones. Despite this limitation, the compound has found some use in synthesis (82TL4995). 

To create a setting favorable for the formation of the E-ring of ginkgolide B, it is first necessary to modify the reactivity potential of ring F in 23. Exposure of a solution of 23 in methylene chloride to 1,3-propanedithiol and titanium(iv) chloride at 0°C results in the formation of dithiane 24 in quantitative yield. Oxidation of the primary alcohol with PDC in the presence of acetic acid gives aldehyde 25 in a yield of 75 %. 

In total synthesis, model studies are frequently performed on simpler systems prior to the final assault on the target molecule. In the synthesis of zaragozic acid A (1), 2-methyl-1,3-dithiane (92) was employed as a simple model for the more elaborate dithiane 67. Deprotonation of 92 with n-butyllithium under standard conditions47 and addition of the aldehyde provides a mixture of two diastereoisomers, 93 and 94 (Scheme 22), in approximately equal amounts. One of the diastereoisomers (93) lacks the TMS group,... 

In ( )-[2-(l-propenyl)-l, 3-dithian-2-yl]lithium, no problem of EjZ selectivity arises. It is easily prepared by deprotonation of the allylic dithiane87,88 with butyllithium in THF, whereas deprotonation of the 2-propylidene-l, 3-dithiane requires the assistance of HMPA. The addition to saturated aldehydes proceeds with excellent y-regioseleetivity and anti selectivity88,89. As often observed in similar cases, aldehydes which bear an, p2-carbon atom adjacent to the carbonyl group give lower selectivities. The stereoselectivity decreases with ketones (2-bu-tanone y/a 84 16, antiisyn 77 23)88. The reaction with ethyl 2-oxopropanoate is merely nonstereoselective90, but addition of zinc chloride improved the syn/anti ratio to 96 4, leading to an efficient synthesis of ( )-crobarbatic acid. 

Table 4. (l,3-Dilhian-2-ylidene)-Subsliluled Alkanols by Addition of (A>[2-( l-Propcnyl)-1,3-dithian-2-yl]lithiuin to Aldehydes... 

Another useful application of this reaction stems from the fact that dithianes can be desulfiirated with Raney nickel (14-34). Aldehydes can therefore be converted to chain-extended hydrocarbons ... 

Other carbanionic groups, such as acetylide ions, and ions derived from a-methylpyridines have also been used as nucleophiles. A particularly useful nucleophile is the methylsulfinyl carbanion (CH3SOCHJ), the conjugate base of DMSO, since the P-keto sulfoxide produced can easily be reduced to a methyl ketone (p. 549). The methylsulfonyl carbanion (CH3SO2CH2 ), the conjugate base of dimethyl sulfone, behaves similarly, and the product can be similarly reduced. Certain carboxylic esters, acyl halides, and DMF acylate 1,3-dithianes (see 10-10. )2008 Qxj(jatjye hydrolysis with NBS or NCS, a-keto aldehydes or a-... 

Alkylation and hydrolysis of imines alkylation of aldehydes 10-107 Alkylation and hydrolysis of dithianes 10-108 Alkylation and hydrolysis of oxazines and similar compounds 10-109 Reaction of diazo aldehydes with boranes... 

Ring enlargement.1 A new route to seven-membered ring systems from a cyclohexenone (1) involves a photocycloaddition of ethylene to provide the bicy-clooctanone 2. Addition of lithio-1,3-dithiane to 2 provides the adduct 3, which on reaction with HgO and HBF4 forms an unstable rearranged hydroxy aldehyde... 

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