Benzyloxymethylation

Dichlorodicyanoquinone (DDQ), CH2CI2, H2O, 40 min, it, 84-93% yield.This method does not cleave simple benzyl ethers. This method was found effective in the presence of a boronate. The following groups are stable to these conditions ketones, epoxides, alkenes, acetonides, to-sylates, MOM ethers, THP ethers, acetates, benzyloxymethyl (BOM) ethers, and TBDMS ethers. 

Benzyloxymethyl Ester (BOM Ester) RCOOCH2OCH2C6H5 (Chart 6) Formation ... 

The related 5-benzyloxymethyl monothioacetal (BOM) has been used for cysteine protection. ... 

Tri.-nethylsilyl triflate (TMSOTf), PhSCH, CF3COOH. These conditions also cleave the following protective groups used in peptide synthesis (MeO)Z-, Bn-, Ts-, CI2C6H3CH2-, BOM (benzyloxymethyl)-, Mts-, MBS-, r-Bu-SR, Ad-SR, but not a BnSR, Acm, or Arg(N02) group. The rate of cleavage is reported to be faster than with TfOH/TFA. 

Methoxymethyl, 27 Methylthiomethyl, 33 (Phenyldimethylsilyl)methoxymethyl, 35 Benzyloxymethyl, 36 p-Methoxybenzyloxymethyl, 37 p-Nitrobenzyloxymethyl, 38 o-Nitrobenzyloxymethyl, 38 (4-Methoxyphenoxy)methyl, 38 Guaiacolmethyl, 39 /-Butoxymethyl, 39 4-Pentenyloxymethyl, 40 Siloxymethyl, 41... 

Methoxymethyl. 257 Benzyloxymethyl, 258 Methoxyethoxymethyl, 258 2-(Trimethylsilyl)ethoxymethyl, 259 Methylthiomethyl, 259 Phenylthiomethyl, 259 Azidomethyl, 260 Cyanomethyl, 260 2,2-Dichloro-1,1-difluoroethyl, 260 2-Chloroethyl, 261 2-Bromoethyl, 261 Tetrahydropyranyl, 261 1-Ethoxyethyl, 261 Phenacyl, 262... 

Fluorenylmethyl, 387 Methoxymethyl, 388 Methylthiomethyl, 389 Tetrahydropyranyl, 390 Tetrahydrofuranyl, 390 Methoxyethoxymethyl, 390 2-(Trimethylsilyl)ethoxymethyl, 391 Benzyloxymethyl, 391 Pivaloyloxymethyl, 391 Phenylacetoxymethyl, 392 Triisopropylsilylmethyl, 392 Cyanomethyl, 392 Acetol, 393 Phenacyl, 393... 

S-Methoxymethyl, 471 S-lsobutoxymethyl, 471 S-Benzyloxymethyl, 472 S-2-Tetrahydropyranyl, 472 S-Benzylthiomethyl, 473 S-Phenylthiomethyl, 473 Thiazolidine, 473 S-Acetamidomethyl, 474... 

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

Through some conventional functional group manipulations, intermediate 5 could be derived from compound 9. Retrosynthetic disassembly of intermediate 9, in the manner illustrated in Scheme 2, furnishes the benzyloxymethyl ether of (/ )-/ -hydroxyisobutyral-dehyde (10) as a potential precursor and introduces the interesting... 

Still s synthesis of monensin (1) is based on the assembly and union of three advanced, optically active intermediates 2, 7, and 8. It was anticipated that substrate-stereocontrolled processes could secure vicinal stereochemical relationships and that the coupling of the above intermediates would establish remote stereorelationships. Scheme 3 describes Still s synthesis of the left wing of monensin, intermediate 2. This construction commences with an aldol reaction between the (Z) magnesium bromide enolate derived from 2-methyl-2-trimethylsilyloxy-3-pentanone (21) and benzyloxymethyl-protected (/ )-/ -hydroxyisobutyraldehyde (10).2° The use of intermediate 21 in aldol reactions was first reported by Heathcock21 and, in this particular application, a 5 1 mixture of syn aldol diastereoisomers is formed in favor of the desired aldol adduct 22 (85% yield). The action of lithium diisopropylamide (LDA) and magnesium(n) bromide on 21 affords a (Z) magnesium enolate that... 

From intermediate 12, the path to key intermediate 7 is straightforward. Reductive removal of the benzyloxymethyl protecting group in 12 with lithium metal in liquid ammonia provides diol 27 in an overall yield of 70% from 14. Simultaneous protection of the vicinal hydroxyl groups in 27 in the form of a cyclopentanone ketal is accompanied by cleavage of the tert-butyldimethylsilyl ether. Treatment of the resultant primary alcohol with /V-bromosuccini-mide (NBS) arid triphenylphopshine accomplishes the formation of bromide 7, the central fragment of monensin, in 71 % yield from 27. 

As inert as the C-25 lactone carbonyl has been during the course of this synthesis, it can serve the role of electrophile in a reaction with a nucleophile. For example, addition of benzyloxymethyl-lithium29 to a cold (-78 °C) solution of 41 in THF, followed by treatment of the intermediate hemiketal with methyl orthoformate under acidic conditions, provides intermediate 42 in 80% overall yield. Reduction of the carbon-bromine bond in 42 with concomitant -elimination of the C-9 ether oxygen is achieved with Zn-Cu couple and sodium iodide at 60 °C in DMF. Under these reaction conditions, it is conceivable that the bromine substituent in 42 is replaced by iodine, after which event reductive elimination occurs. Silylation of the newly formed tertiary hydroxyl group at C-12 with triethylsilyl perchlorate, followed by oxidative cleavage of the olefin with ozone, results in the formation of key intermediate 3 in 85 % yield from 42. 

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