Oxazoles, silylated

The N-silylated enol acetate 1523 is cyclized by TMSOTf 20 in CHCI3, in 95% yield, giving the oxazole 1524 [57]. The dimeric derivative 1525 affords the 2,2 -bis-oxazole 1526 in 46% yield [57]. 2-Benzoylamino-3-chloropyridine 1527 is cyclized by polyphosphoric acid trimethylsilyl ester (PPSE) 195 on heating for 15 h in boiling 1,2-dichlorobenzene to give 40-60% 2-phenyloxazolo[5,4-f)]pyridine 1528 [58] (Scheme 9.34). 

Interestingly, deprotonation of the 3-oxo-pyrrolo[l,2-f]oxazole 277 with r-BuLi at —78°C took place at the C-5 position. Addition of an electrophile provided the substituted products 278 in good yields. Stannyl and silyl chlorides, dimethyl sulfate, ketones, and benzaldehyde were successfully used as electrophiles. A significant feature of this lithiation-substitution reaction is the generally high Ar-diastereoselectivity only single diastereomers of products were isolated (Scheme 41) <2001JA315>. 

Oxamidobis-ethyl(3,5-di-tert-butyl-4-hydroxyhydrocinnamate), 3 115 Oxane bonds, silylation and, 22 702-703 Oxazine soluble dyes, 7 373t Oxaziridines, 9 372-373 2-Oxazolines, microwave-assisted synthesis of, 76 576 Oxazoles, 27 151... 

The reaction of acylsilanes with acid chlorides in the presence of A1C13 leads to furans (Table 9.41) [45]. In these reactions an acyl cation initiates the addition with ensuing silyl migration yielding an intermediate vinyl cation. Attack of the carbonyl oxygen followed by proton loss affords the observed products (Scheme 9.16). An analogous reaction with nitrosyl fluoroborate provides a route to oxazoles (Table 9.42) [65]. The nitrosyl cation serves as the electrophile in this application. 

Silicon protection is also commonly used to direct lithiation chemistry in five-membered heterocycles. For example, oxazoles , thiazoles and Ai-alkylimidazoles ° ° lithiate preferentially at C-2, where the inductive effect of the heteroatoms is greatest. If C-2 is blocked, lithiation occurs at C-5, where there is no adjacent lone pair to destabilize the organolithium. Functionalization of these heterocycles at C-5 can therefore be achieved by first silylating C-2, reacting at C-5 and then removing the silyl group. The synthesis of 666 illustrates this sort of sequence (Scheme 258) °. ... 

The trialkylstannyl derivatives are obtained directly by reaction of tri-methyltin chloride with 2-lithiooxazole (87S693), but in the case of the silyl compounds an extra step is required, involving the base-catalyzed thermal ring closure of the silylated ring-opened oxazole (Scheme 81)(84CC258 87JOC3413). 

With thiazolines it is still possible to obtain silylated heterocycles, despite the initial reaction giving the ring-opened product, since like the situation with oxazole (Section II1,B, 1) the desired isomerization can be induced thermally (Scheme 140) [90H(31)1213]. However, the analogous isomerization cannot be induced in the oxazoline case (87S693). 

Diazocarbonyl compounds can also be prepared by C-acylation of diazoalkanes with polystyrene-bound acyl halides (Entry 6, Table 10.19). As an alternative to diazomethane, the more stable a-(trimethylsilyl)diazomethane may be used, which is sufficiently nucleophilic to react with acyl halides. On heating, the resulting a-(trimethyl-silyl)diazo ketones undergo Wolff rearrangement to yield ketenes, and have also been used as starting materials for the preparation of oxazoles [368]. 

Transition-metal catalyzed transfer of acylcarbenes to nitriles leads to 1,3-oxazoles via nitrile ylide intermediates123. The corresponding nitrile ylide chemistry derived from acyl(silyl)carbenes still awaits a closer look, but it has been shown that the rhodium-catalyzed decomposition of 198 in the presence of methyl cyanoformate and benzaldehyde provides 1,3-oxazole 221 (equation 71) exclusively120. This implies that the carbene moiety has been transferred only to the nitrile but not to the aldehyde. 

This type of C-H carbonylation is also feasible at C-H bonds in five-membered N-heteroaromatics, such as imidazoles 3 (Scheme 2), thiazoles 5, oxazoles 6, and pyr-azoles 7 [3], Functional group compatibility was extensively studied in the reaction of 3, and it was found that a variety of functional groups, for example ketone, ester, cy-ano, acetal, N, O-acetal, ketal, and silyl groups, were tolerated under the reaction conditions, indicating that C-H carbonylation reactions have now reached a satisfactory level in organic synthesis. The reactivity of the five-membered N-heteroaromatics is significantly affected by the pK, of conjugate acid of the N-heteroaro-... 

The addition of carbonylated electrophiles to the 2-lithio derivative of 4-oxazolinyloxazole 132 allowed the efficient preparation of 5-phenyloxazoles 134 bearing a variety of hydroxyalkyl groups at C-2 position and a carboxyl (or formyl) function at C-4. This protocol suppresses the troublesome electrocyclic ring-opening reaction and allows access to the target compounds by simple chemical transformation of the oxazoline moiety of 133 <02JOC3601>. A direct chemoselective C-2 silylation of oxazoles was performed by treatment of the lithiated parent compounds with silyl triflates <02TL935>. 

Lithiooxazoles exist in equilibrium with their open chain forms one solution for the synthesis of 2-substituted oxazoles involves 2-silylation (and then reaction with an electrophile). By correct choice of silylating agent, it is possible to trap the ring-closed or ring-opened forms (Scheme 58) <2002TL935>. 

Methan Pyrrolo-(2-trimethylsilyl-ethoxy)- E14a/2. 162 (Cl -> N) 1,2-Oxazol 3-tert.-Butyl-5-trimethyl-silyl- E8a, 65 [(H3C)3C-CO-C = C —SiR3 4- H2N-OH]... 

The additives (MeaSiCl or BF3 Et20) may activate the carbonyl compound or stabilize the intermediate. BF3 Et20 has been used as an activator in the reaction of aldehydes with lithiated phenylsulfones [111] although its fimc-tion remains vague. It may be noted that acyclic products were formed on silylation of the hydroxy sulfides obtained in the reaction of oxazol-2-yl sulfides with aldehydes [80]. 

Silyl oxazoles 55 have been used as precursors to 4-halooxazoles 56, which can then serve as coupling partners in Pd-catalyzed Sonogashira coupling reactions <2000SL692>. The silylated oxazole 55 was prepared in good yield by a Huisgen oxazole synthesis which involved a rhodium-catalyzed reaction between ethyl (triethylsilyl)diazoacetate 54 and benzonitrile (Scheme 7). 

A number of techniques have been employed to alleviate this issue such as complexation of the electron pair on nitrogen of the heterocycle with a Lewis acid prior to C-H deprotonation, and the use of C-2 silyl-oxazoles which tend to react as a coupling partner via the ring-closed form. 

In more specific work, adducts of the form TiCl4Lo have been prepared and reported. These include complexes where L = TMEDA,16 benzotriazole,17 benzothiazole,18 2-aminobenzimidazole,19 2-methyl-2-oxazoline, thiazole and a variety of oxazole-derivatives.20 Similarly, complexes of the form TiCl4L (L = RC6H4NH2, R=Bu , Cl, N02, Me21,22 isoxazole, 5-methylisoxazole,20 2-aminobenzimidazole, 2(2 -aminophenyl)benzimidazole,19 2-pyridylphenylacetonitrile22) have been reported. Schifif base adducts of TiCl4 derived from A-methylpyrrole-2-carboxaldehyde, 4-methyl-benzaldehyde, salicylaldehyde, and aromatic or aliphatic amines have also been characterized.23-25 A variety of 2 1 substituted silyl-amine-Ti adducts have also been reported 26-28... 

The synthetic utihty of phenyliodooxazole 76 was demonstrated through a Sonogashira coupling with alkylacetylene and silanes, 4-Alkynyl- and silylated-oxazoles 77 were prepared in moderate yields [51],... 

Asymmetric Aldol Reaction Although several examples showed that reaction rates with aluminum reagents exceed those with silyl cations, direct reflection on this basis to the corresponding asymmetric reaction remains challenging [8]. Apart from the Mukaiyama aldol reaction, an alternative reaction candidate was oxazole... 

Substitution by carbon and sulfur electrophiles at the 2-position may be achieved by activation of oxazole with a 2-trimethylsUyl group. For example, 4-methyl-2-trimethylsilyloxazole (49) reacts with aldehydes to give silyl ethers, it reacts with acyl chlorides to give acyl derivatives, and it reacts with phenylsulfenyl chlorides to give a mixtm-e of 2-phenylthio and 2,5-di(phenylthio)oxazole <87JOC34l3>. Reactions with two a-chiral aldehydes, (R)-2,3-0-isopropylideneglyceraldehyde and... 

Synthesis of 7 -amino acid-oxazole fragment 68 of calyculins A and B from D-erythronol-actone 58 has been reported by conversion to 59," which was subjected to oxidation reaction to afford the hemiaminal 60 (Scheme 9) Acetylation of 60 furnished 61, which was converted to ketone 62 in 88% yield. Conversion of 62 to a silyl enol ether, ozonolysis with reductive workup and O-methylation of the resultant alcohol 63 furnished 7 -lactam 64. Treatment of 64 with CAN led to 65 (60%), which was reacted with (CHj)2 A1 derivative of 66 to provide 67 (62%), which upon removal of the silyl group provided 68. 

Sodium dialkyl phosphites add to the 4-arylidene-4,5-dihydro-1,3-oxazoles 273 to give the enolate anions 274 on the other hand, the adducts 275—the potential products of the silylation of 274—are more conveniently obtained by additions of dialkyl trimethylsilyl phosphite. The adducts 275 undergo alcoholysis with alcohols, R OH, to give the 2-amino-3-phosphinoylpropanoic acid esters 276, whilst the action of water yields the acids 276... 

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