A-Silyloxy

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

Stereoselectivities of 99% are also obtained by Mukaiyama type aldol reactions (cf. p. 58) of the titanium enolate of Masamune s chired a-silyloxy ketone with aldehydes. An excess of titanium reagent (s 2 mol) must be used to prevent interference by the lithium salt formed, when the titanium enolate is generated via the lithium enolate (C. Siegel, 1989). The mechanism and the stereochemistry are the same as with the boron enolate. 

In a cross-coupling benzoin condensation of two different aldehydes, usually a mixture of products is obtained, with the ratio being determined by the relative stabilities of the four possible coupling products under thermodynamic control. If, however, an acyl silane, e.g. 5, is used as the donor component, the a-silyloxy-ketone 6 is obtained as a single product " ... 

The nucleophilic acylation of 2-phenylpropanal or 3-phenyI-2-butanone with cyano(trimethyl-silyloxy)phenylmethyllithium proceeds with high Cram selectivity6. The primary addition product 7, after silyl migration and loss of lithium cyanide, gives the a-silyloxy ketones 86. 

Only moderate induced diastereoselectivity is achieved in the addition reactions of lithium enolates of the following a-silyloxy ketones43 and carbohydrate-derived ketones44, deproto-nated in each case at the methylene group in a regioselective manner to benzaldehyde. 

Kim and coworkers introduced silyl radical mediated addition of alkyl radical to silyloxy enamine 76. The silyloxy enamine moiety is readily accessible from a variety of functionalities. The mechanistic concept is illustrated in the Scheme 12 and involves the addition of R radical to 76 to give the radical adduct 77 and the subsequent homolytic cleavage of N-O bond to yield the desired product 78 and a silyloxy radical 79. The latter undergoes 1,2-phenyl migration to give the silyl radical 80 that abstracts halogen from the alkyl halide to regenerate the R radical. 

Silyltitanation of 1,3-dienes with Cp2Ti(SiMe2Ph) selectively affords 4-silylated r 3-allyl-titanocenes, which can further react with carbonyl compounds, C02, or a proton source [26]. Hydrotitanation of acyclic and cyclic 1,3-dienes functionalized at C-2 with a silyloxy group has been achieved [27]. The complexes formed undergo highly stereoselective addition with aldehydes to produce, after basic work-up, anti diastereomeric (3-hydroxy enol silanes. These compounds have proved to be versatile building blocks for stereocontrolled polypropionate synthesis. Thus, the combination of allyltitanation and Mukayiama aldol or tandem aldol-Tishchenko reactions provides a short access to five- or six-carbon polypropionate stereosequences (Scheme 13.15) [28],... 

Oxidation of silyl enol ethers. Oxidation of silyl enol ethers to a-hydroxy aldehydes or ketones is usually effected with w-chloroperbenzoic acid (6, 112). This oxidation can also be effected by epoxidation with 2-(phenylsulfonyl)-3-( p-nitrophenyl) oxaziridine in CHC1, at 25-60° followed by rearrangement to a-silyloxy carbonyl compounds, which are hydrolyzed to the a-hydroxy carbonyl compound (BujNF or H,0 + ). Yields are moderate to high. Oxidation with a chiral 2-arene-sulfonyloxaziridine shows only modest enantioselectivity. 

Addition to carbonyl compounds. In the presence of ZnCl2 or SnCl2, N,Si(CH,), adds to aldehydes or ketones to form gem-di azides. Reactions catalyzed by NaN and 15-crown-5 provide a-silyloxy azides exclusively. The adducts of aldehydes in both reactions are obtained in higher yield than the adducts of ketones. 

Rearrangement of epoxy silyl ethers. When treated with 1 equiv. of TiCl4, a-silyloxy epoxides rearrange to p-hydroxy carbonyl compounds. 

In order to proceed according the outlined synthetic plan, a C(10)-a silyloxy substituent was used in the ketone 38 as a conformational control element which... 

Silyl enol ethers have been prepared via a Brook rearrangement from the reaction of phenyldimethylsilyllithium with a-silyloxy ketones (see Scheme 68). The comparison of the rate of the base-catalysed Brook rearrangement in -substituted... 

The a-silyloxy alkyl radical generated by the addition of (TMS)3Si radical to the aldehyde moiety of 45 has been employed in radical cyclization of (3-aminoacrylates (Reaction 7.53) the trans-hydroxy ester and the lactone in a 2.4 1 ratio were the two products [62]. 

Rearrangement of a-silyl oxyanions to a-silyloxy carbanions via a reversible process involving a pentacoordinate silicon intermediate is known as the [l,2]-Brook rearrangement, or [l,2]-silyl migration. 

On thermolysis, appropriately substituted A-allyl-A-silyloxy enamines 19 undergo smooth [3,3]-sigmatropic rearrangements to the corresponding A-silyloxy imino ethers laP (equation 5). Two stereogenic centers are created but no reference to chiral induction is referred. High diastereoselectivity was observed and short reaction times favoured the syn A-silyloxy imino ether diastereomers. 

TABLE 2.8. CHARACTERISTIC C NMR RESONANCES FOR A-SILYLOXY NITROSO ACETALS... 

A -Silyloxy isoxazolidines can be converted to the corresponding isoxazolines by elimination of R3SiOH. The NMR spectra of the corresponding isoxazolines retain the chemical shift of the HC(5), however, a downfield shift is observed for HC(3), as well as C(3), Tables 2.9 and 2.10 (18,36). The IR spectra return to a range similar to that of the original silyl nitronate (Fig. 2.8). 

The A-silyloxy-isoxazolidine (XIX) provides several opportunities for further elaboration. One of the more common transformations is the elimination of silanol from the isoxazolidine (Scheme 2.9), which results in the formation of isoxazolines (XX), which are also prepared from the [3 + 2] cycloaddition of nitrile oxides... 

Ausbeute bezogen auf Keton als Vorstufe des a-Silyloxy-carbonsa u re-nitrils... 

Enyne 7a having a silyloxy group on the alkyne gives cyclic compound 8a having a vinyl silyloxy moiety, which is converted into methyl ketone 9a by desilylation. In a similar manner, enyne 7b affords bicyclic methyl ketone 9b in 68% yield after deprotection of the silyl group. However, ynoate 7c and yne-phosphonate 7d do not give cyclized compounds. Ene-ynoate 12, which is obtained by treatment of enol ether 11 with BuLi affords cyclic enol ether 13 in good to moderate yields " (Scheme 4). 

Isomerization of a-silyloxy and a-alkoxyallyl stannanes using either BF3-OEt2 or lithium perchlorate (UCIO4) affords (Z)-y-siloxy- and y-alkoxyallylic stannanes. Treatment with Yb(OTf)3 affords mixtures of (Z)- and (E)-y-siloxy- and y-alkoxyallylic stannanes. See Marshall, J. A. Jablonowski, J. A. Elliott, L. M. J. Org. Chem. 1995, 60, 2662. 

Reduction of a-alkoxy ketones.2 a-Hydroxy ketones are reduced by Sml2 in THF/CH3OH in rather low yield ( 30%). In contrast a-acetoxy ketones are reduced in >75% yield. A simple expedient is to reduce the a-hydroxy ketone in the presence of AczO with Sml2 (equation I). a-Silyloxy, benzoyloxy, and tosyloxy... 

The oxyanion of the enolate (or a silyloxy group) appears to speed up this reaction relative to an unadorned Claisen system, but an even more dramatic acceleration is seen when Cope systems have an oxyanion substituent on the tetrahedral carbon, as in the reaction 5.59 —> 5.61, which takes place at a... 

A number of acyl trimethyl silanes chiral at the a- or -carbon atom have been prepared in non-racemic form. Chiral a-alkoxy and a-silyloxy acyl silanes have been generated in very high yields by oxidative rearrangement of enantiomerically pure silyl epoxides, induced by dimethyl sulphoxide and silyl triflates (Scheme 32)112. 

Cycloaddition reactions of acyl silanes appear to be rare, but Brook has shown that a-silyloxy bis(trimethylsilyl)silenes (52), generated photochemically from acyl tris(trimethylsilyl)silanes (vide infra, Section IV.A.4), undergo [2 + 2] and [4 + 2] cycloaddition reactions with ketones, and [4 + 2] cycloaddition reactions with less bulky acyl silanes, as illustrated in Scheme 8717,24 26 72 73,201. They do not, however, react with their parent acyl tris(trimethylsilyl)silanes. 

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