Aldehydes 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. 

Cram erythro-products" (G.E. Keck, 1984 A, B, C). [3-(Silyloxy)allyl]stannanes and O-pro-tected a- or y -hydroxy aldehydes yield 1,2,3- or 1,2,4-triols with three chiral centres with high regio- and diastereoselectivity (G.E. Keck, 1987). 

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 " ... 

When a mixture of aldehydes and (Z)-l-ethylthio-l-trimethylsilyloxy-l-propene is added slowly to a solution of tin(Il) triflate and 10-20 mol% of the chiral diamine 4 in acetonitrile, /1-silyloxy thioesters 5 are obtained in high simple diastereoselection and induced stereoselectivity. Thus, the chiral auxiliary reagent can be used in substoichiometric amount. A rationale is given by the catalytic cycle shown below, whereby the chiral tin(II) catalyst 6 is liberated once the complex 7 has formed33. 

Our group has exploited 4-phenylthio-l,3-dioxanes as convenient precursors to 4-lithio-l,3-dioxanes [45,65-69]. 4-Phenylthio-l,3-dioxanes 184 were originally prepared from -silyloxy aldehydes 183 [65] (Eq. 28). Lewis acid-promoted addition of phenylthiotrimethylsilane gave an unstable thioacetal intermediate, which could be converted in situ to the corresponding 1,3-dioxane. Yields for this process are variable, as the product is unstable under the conditions of its formation. The reaction slowly evolves to a mixture of the desired product, the phenylthio acetal of 183, the phenylthio acetal of acetone, and a variety of other unidentified products. 

The potential for coordination depends on the oxy substituents.82 Alkoxy substituents are usually chelated, whereas highly hindered silyloxy groups usually do not chelate. Trimethylsiloxy groups are intermediate in chelating ability. The extent of chelation also depends on the Lewis acid. Studies with a-alkoxy and (3-alkoxy aldehydes with lithium enolates found only modest diastereoselectivity.83... 

Several variations of the Peterson reaction have been developed for synthesis of alkenylsilanes.80 -P-Arylvinylsilanes can be obtained by dehydration of (3-silyloxy alkoxides formed by addition of lithiomethyl trimethylsilane to aromatic aldehydes. Specific Lewis acids have been found to be advantageous for the elimination step.81... 

A. y-Oxygen-Substituleel Stannanes. Oxygenated allylic stannanes have been synthesized and used advantageously in several types of syntheses. Both a- and y-alkoxy and silyloxy stannane can be prepared by several complementary methods.177 C-y-Alkoxy and silyloxy allylic stannanes react with aldehydes to give primarily syn... 

Silyloxy)alkenes were first reported by Mukaiyama as the requisite latent enolate equivalent to react with aldehydes in the presence of Lewis acid activators. This process is now referred to as the Mukaiyama aldol reaction (Scheme 3-12). In the presence of Lewis acid, anti-aldol condensation products can be obtained in most cases via the reaction of aldehydes and silyl ketene acetals generated from propionates under kinetic control. 

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. 

In the Mukaiyama cross-aldol reaction, an aldehyde and a ketene silyl acetal [e.g. (43)] react via Lewis acid catalysis to give a jS-silyloxy ester (44). The reaction... 

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]. 

If further acidic C—H bonds in the molecule cause problems, the tin-trick can be applied. The asymmetric deprotonation of a bifunctional carbamate (39a) is accomplished at an early stage and the masked carbanionic centre carried through the synthesis as a stan-nyl group. For instance, the (S)-5-silyloxy-l-tributylstannyl-pentyl carbamate 39b (> 95% ee) was produced by the usual means and converted by standard steps via the aldehyde 78 into the allyl chloride 79 (equation 17) . Lithiodestannylation of 79 by n-BuLi proceeds faster than reductive lithiation in the allylic position to form the lithiocarbamate 80,... 

When 2-aza-3-silyloxy-l,3-diene 336 was heated with aliphatic or aromatic aldehydes in toluene, stereoisomeric tetrahydro-l,3-oxazin-4-one derivatives 200 and 337 were obtained without Lewis acid catalysis (Equation 34). The cycloaddition proved to be highly diastereoselective in favor of the OTr/o-adducts, leading to the >-isomers 200 as the main products <1999TL7079, 2002S2043>. 

Hudlicky and Barbieri (178) developed a simple procedure to synthesize the substituted vinyl oxiranes by adding the lithium dienolate of a l-bromo-4-silyloxy-ethyl-2-butenoate to substituted aldehydes. From the vinyl oxiranes formed. 

Normant and Poisson prepared allenylzinc bromide reagents from TMS acetylenes along the lines of Epsztein and coworkers5, by sequential lithiation with s-BuLi to yield a lithiated species, and subsequent transmetallation with ZnBr2 (equation 35)27,28. Additions to racemic /J-silyloxy aldehydes proceed with low diastereoselectivity to afford mixtures of the anti,anti and anti,syn adducts (Table 17). The latter adducts are formed via an anti Felkin-Anh transition state. Additions to the racemic IV-benzylimine analogs, on the other hand, proceed with nearly complete Felkin-Anh diastereoselectivity to yield the anti,anti amino alcohol adducts (Table 18). 

The key observation was that L-proline would catalyze the addition of a-hetero aldehydes to a-branched aldehydes such as 2 to give the aldol product 3 with high cnantio- and diastereocontrol. Even more exciting, in the absence of other acceptors the a-hetero aldehydes dimerize with high relative and absolute stereocontrol. Both alkoxy and silyloxy aldehydes worked efficiently. 

Homo-Reformatsky reaction.1 The reaction of 1-ethoxy-1-trimethylsilyloxy-cyclopropane (1) with an aldehyde in the presence of ZnCl2 results in y-silyloxy esters via a zinc homoenolate (a) of ethyl propionate (equation I). Znl2 is the preferred catalyst in the case of reactions with acetophenone and benzaldehyde dimethyl acetal and in reactions of l-isopropoxy-l-(t-butyldimethylsilyl-oxy)cyclopropane with aromatic aldehydes. 

Nucleophilic phosphonylations of w-silyloxy aldehydes (e.g. 77) with phosphite 78 give a mixture of 79 and 80 with moderate to good diastereoselectivity (equation 36)55. The ratio of 79/80 depends greatly upon the size of the silyl groups in 77, according to the order shown in entry 42 of Table 1. 

Silyloxy-2-aldehydes can undergo hetero-Diels-Alder reaction with aldehydes to give useful heterocycles.350 A model reaction, H2C=C(OSiH3)-N=CH2 with formaldehyde, has been explored theoretically. Lewis acids such as boron trifluoride catalyse the reaction by coordinating to the aldehyde oxygen, making the aldehyde more electrophilic. Concerted and stepwise mechanisms for this process are considered. 

The chiral imidazolidinone 45 also catalyzes the Mukaiyama-Michael reaction between 2-silyloxy furans and a,/ -unsaturated aldehydes, affording enantiomeri-cally highly enriched y-butenolides (Scheme 4.18) [33]. For optimum catalytic performance, hydroxyl additives are necessary, and addition of 2 equiv. water proved best. 

In a synthesis of (+)-hyptolide Marco exploited the Carreira procedure for alky-nylation of a /3-silyloxy aldehyde to afford the product proparyl alcohol as a single isomer [28], Subsequent semireduction of the alkyne furnished the requisite Z double bond to complete the synthesis (Eq. 23). 

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