2- Acyl-1,3-oxathianes

Reversal of diastereoselectivity of reactions with RMgX and RLi.1 The chiral 2-acyl- 1,3-oxathiane 1 (12, 237-239) undergoes diastereoselective addition of... 

The reduction of 2-acyl- 1,3-oxathianes such as 3.96 (X = S) or of 2-acyl-3-oxa-N-benzylpiperidines 3.96 (X = NCH2Ph) can also take place with or without chelation control [El, EFl, EH2, KEl, KF4]. In cases of chelation control, the oxygen atom of the heterocycle participates in the chelation process (Figure 3.32). When the reaction is carried out with Li(5-Bu)3BH in the presence of Lil as an additive, the reduction occurs under chelation control. However, when using two equivalents of DIBAH, each of them coordinates to a one basic site, and no chelation takes place. The use of these chiral auxiliaries allows the synthesis of nonracemic a-hydroxyaldehydes or a-hydroxyesters with a high enantiomeric excess [NNl, S3]. 

The addition of a variety of organometallic reagents to imines and hydrazones (74) of 2-acyl-1,3-oxathianes derived from pulegone proceeds with very high diastereoselectivity (Equation (39)), the addition of lanthanide salts reversing the sense of asymmetric induction <90JA8189,94CL831). 

Deprotonation of oxathiane 16 with butyllithium, addition of an appropriate aldehyde and subsequent oxidation lead to the acylated oxathianes 17 which can be used in diastereose-lective nucleophilic addition reactions. 

Oxathiane 101 is readily deprotonated using s-BuLi, and the resulting anion reacts with alkyl halides, ketones, and benzonitrile (85JOC657). The majority of work in this area, however, is due to Eliel and coworkers and has involved chiral 1,3-oxathianes as asymmetric acyl anion equivalents. In the earliest work it was demonstrated that the oxathianes 102 and 103, obtained in enantiomeri-cally pure form by a sequence involving resolution, could be deprotonated with butyllithium and added to benzaldehyde. The products were formed with poor selectivity at the new stereocenter, however, and oxidation followed by addition... 

Besides 1,3-oxathianes, the 1,3-dithiane 1-oxide moiety can be used for directing the nucleophilic addition of an organometallic reagent to a carbonyl group in a diastereoselective manner. The addition of methylmagnesium iodide to the 2-acyl-l,3-dithiane 1-oxide 23A leads exclusively to the diastereomer which is formed by Re-side attack. On the other hand, addition... 

Eliel s oxathiane auxiliary was used for stereoselective transformations and has been reviewed in part <2003H(60)1477>. As expected, reaction of the lithiated auxiliary with acetaldehyde gave the addition product with low stereoselectivity at the side-chain stereocenter <1997M201>. Better stereocontrol was observed, when methyl Grignard reagent was added to 2-acyl-l,3-oxathiane <2000JCCS63>. Reaction of 2-vinyl-l,3-oxathiane with 1,1-diphenylethene, mediated by TiCU, afforded dihydrothiopyrans in 82% yield, albeit with low enantioselectivity (Scheme 84) <2003T1859>. 

New chiral auxiliaries for nucleophilic reactions have been prepared from 5-hydroxy-l-tetralone <2001TA2605> and myrtenal <2001TA3095> and their use in diastereoselective reactions has been evaluated. It was found that both the tetralone- <2003EJ0337, 2003JOC6619> and the myrtenal- <2003TA3225, 2005TA1837> derived 2-acyl-l,3-oxathianes reacted diastereoselectively with nucleophiles (Equations 60 and 61). 

Interestingly, even the simple 2-acyl-l,3-oxathiane 193 containing just a methyl group at C-6 reacts with N,N-dimethylbromoacetamide/Sml2 to give the addition product in excellent yield (96%) and diastereoselectivity (99 1) (Equation 62) <2003CH38>. 

A reversal of the stereochemical outcome of the reduction of 2-acyl-l,3-oxathianes was demonstrated when the 1,3-oxathiane 3-oxide instead of 1,3-oxathiane was treated with chelating reducing agents, such as L-selectride (Equation 63) <1998BKC911>. 

Stereoselective synthesis of oxathiane tertiary carbinols (8, 508-509). This reagent is now preferred over the isomeric 4,6,6-trimcthyl-l,3-oxathiane (8, 508-509) for a two-step, highly stereoselective synthesis of oxathiane tertiary carbinols (3, equation I), which can be cleaved to enantiomerically pure tertiary a-hydroxy aldehydes. The first step, acylation with retention of configuration, gives the more stable equatorial adduct 2... 

Several other acyl anions or potential acyl anion equivalents bearing at least one nonoxidized sulfur atom have since been proposed, and some of them have been alkylated successfully. This is effectively the case for the following metallated compounds (i) yV-methylthioformaldine (Scheme 73, entry c) (ii) 1,3-oxathianes, and a-trimethylsilylmethyl analogs (iii) a-methoxythioanisole (Scheme 74, entry a Scheme 75, entry the parent compound also allows the synthesis of acetals (on acid-... 

Most of the chemistry associated with this series of heterocycles is a consequence of the acetal moiety. For example, all three saturated systems undergo acetal hydrolysis, the dioxanes being the most acid-sensitive. The chemistry of 1,3-dithianes and 1,3-oxathianes is further dominated by the acidity of the C-2 protons, leading to the use of the derived carbanions as acyl anion equivalents, particularly in the case of 1,3-dithiane derivatives. Oxidation at sulfur is also a common process. 

The commonly encountered C-2 anions derived from 1,3-dithiane and 1,3-oxathiane and their derivatives can be generated by treatment with any of a wide range of bases, but typically n-butyllithium (for 1,3-dithianes) or yec-butyllithium (sometimes necessary for 1,3-oxathianes). There are many instances where the deprotonated heterocycles have been used in synthesis, usually as acyl anion equivalents <8977643, b-95MI 608-05>. Use of 1,3-dithiane derivatives is by far the most common, and the derived anions react with with a very wide variety of electrophiles <69AG(E)639, 8977643), whether or not the dithiane system is initially substituted at C-2. For example, 2-lithio-... 

Like the 1.3-dithianes, L3-oxathiane can be metallated with alkyllithium reagents and they hydrolyse about 10,000 times faster with protic acids. However, their value is diminished by the limited stability of the lithio derivatives and their inherent lack of symmetry which introduces the complications of diaster-eoisomerism. Eliel and co-workers have exploited the diastereoisomerism of L3-oxathianes imbedded in asymmetric synthesis [Scheme 2.98]. By relying on the differential Lewis basicities of the oxygen and sulfur atoms in the 2-acyl-13 ... 

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