Acetate, diastereoselective synthesis

A diastereoselective synthesis of /3-(iV-acylamino)aldehydes was accomplished via ruthenium-catalyzed isomerization of 0-vinyl-iV,0-acetals followed by rearrangement in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) (Scheme 36).63... 

In 1986, Evans and colleagues introduced tetramethylammonium triacetoxyboro-hydride, a mild reducing reagent for the highly diastereoselective synthesis of 1,3-anft-diols from acyclic (3-hydroxy ketones1 (Scheme 4.2a). The reaction, commonly called the Evans-Chapman-Carreira reduction, is typically carried out in a 1 1 mixture of anhydrous acetic acid and acetonitrile, as the reaction needs to be run at low temperature in the presence of acetic acid. An important observation is that the anti -diastereoselectivity is realized regardless of the stereochemistry of the a-alkyl substituent Both anti - and. vvn-a.-methyl-(3-hydroxy... 

A double iodoetherification of C2-symmetric acetals has been used for the desymmetrization of 1,6-dienes in an asymmetric total synthesis of rubrenolide (Equation 78) <2005AGE734>. Remarkably, four stereogenic centers have been installed in one reaction step. Stereoelectronic effects in the diastereoselective synthesis of 2,3,5-trisubstituted tetrahydrofurans via iodoetherification have been studied in detail, and I(2,4,6-collidine)2C104 proved to be an efficient reagent for highly stereoselective iodoetherifications <20010L429>. 

Quartromicins are complex C2 symmetric macrocyclic natural products that have significant activity against a number of human viral targets.The diastereoselective synthesis of the endo- and exo-spirotetronate subunits of the quartromicins was accomplished by W.R. Roush and co-workers. The preparation of the exo-a-acetoxy aldehyde involved the Pummerer rearrangement oi a sulfoxide using acetic anhydride as the activating reagent and NaOAc as the co-catalyst. The yield of this transformation was modest and all attempts to improve its efficiency failed. 

Aldehydes, acetals, aminoacetals, and hemiaminals bearing a phenylsilyl or vinyl-silyl group undergo intramolecular phenylation or vinylation on treatment with a Lewis acid [527-530]. The reaction of a-vinylsiloxy- and a-phenylsiloxy-substituted aminoacetals is suitable for highly diastereoselective synthesis of / -aminoalcohols (Scheme 10.201) [529],... 

The ketene 0,0-acetals 83 were prepared from the corresponding bromo derivatives by reaction with strong base A diastereoselective synthesis of the trans- and cis 84 was carried out. Condensation of substituted aminothiophenols and 2-arylidene-l-tetralone afforded 1,4-thiazepines 85. Condensation of o-phenylenediamines with P-ketoesters or 1,1,1-trifluoromethyl-3-(isobutoxymethylene)-2-propanones gave 84. ... 

These transformations can be applied to the stereoselective synthesis of several other carbo- and heteropolycyclic dienes, and are therefore regarded as a model system for the diastereoselective synthesis of steroid and alkaloid compounds47 53,68 70. Thus, estradiol is obtained via intramolecular cocyclotrimerization of a linear enediyne, with silyl- and acetal-protecting groups, which again preferentially leads to one stereoisomer of the primary diene complex 646. 

A diastereoselective synthesis of pyranothiazoles 66 was achieved in a one-pot reaction of the three components glycine, acetic anhydride, and 5-arylidenerhoda-nines 64 by employing MWI under solvent-free conditions. The yields of 66 were 73-86%, compared to 35 3% obtained from conventional heating. The formation of pyranothiazoles 66 occurred through the cyclization of Michael adducts 65... 

A strategy developed by Tietze and coworkers early in his independent career involved the application of intramolecular or intermolecular inverse electron demand hetero-Diels-Alder reactions to iridoid total synthesis. The intermolecular [4+ 2]-cycloaddition of ethyl vinyl ether and unsaturated aldehyde 31 provided acetal 32, which underwent double bond isomerization to afford 33 (Scheme 1) An intramolecular variant of this reaction is discussed in detail later (Scheme 10). More recently, Jacobsen and Chavez extended this work with the enantio- and diastereoselective synthesis of a range of iridoid natural products. Utilizing tridentate Cr(III) catalyst 34, acetal 35 was prepared in 98% ee with good diastereoselectivity (Scheme 1)P... 

Intramolecular 1,3-dipolar cycloaddition has been employed for the synthesis of various natural products as well. For instance, Mateos et al. reported a diastereoselective synthesis of the model insect antifeedant 281 related to 12-hydroxyazadiradione utihzing the intramolecular nitrile oxide cycloaddition (Scheme 65) [167]. The nitro compound 279 was synthesized from a-cyclocitral 278 in four steps. The cleavage of isoxazoline 280 was performed under three different conditions Raney Ni-mediated cleavage in methanol-water-acetic acid provided the epimeric ketoalcohol 282 in 5 3 ratio. While there was 100% selectivity in favor of the axial alcohol 282a in the presence of Pd/C and boric acid, the selectivity was in favor of the equatorial alcohol 282b when boric acid was replaced by acetic acid. 

The diastereoselective synthesis of spirofurooxindoles has been described based on the three-component reaction involving intermolecular carbonyl ylide dipole 23 [69]. The reaction of 3-diazoindol-2-one 21, benzaldehyde and DMAD in the presence of 0.5 mol % of rhodium(II) acetate catalyst furnished the spirofurooxindole 22 (Scheme 7). On the basis of the diastereoselectivity of these reactions, the conformation of the intermolecular carbonyl ylide 23 is provided. In the absence of dipolarophiles, the carbonyl yhde underwent electrocyclization to yield oxiranes 24 [70]. 

It has been observed that in basic media aromatic hydrocarbons and benzylmethyl ethers bound to -Cr(CO)3 are easily nitrosated at the benzylic position. A review type article discusses the stereoselective manipulation of acetals derived from o-substituted benzaldehyde chromium tricarbonyls. The diastereoselective synthesis of a range of substituted cyclohexadienes has been reported from enandomerically pure (2-phenyl-4,S-dibydroxazole)chromium tiicaibonyl complexes. Aromatic nucleophilic substitution on halaogenoarene tricarbonylchromium complexes gives rise to a series of complexed aniline derivatives. The diastereoselective 1,4-addition of organocuprates to o-substituted-phenyI-(E)-enone chromium carbonyl conq)lexes provides a new method for remote stereocontrol at the 1,3, and S-positimis of the side chains. ... 

An efficient and diastereoselective synthesis of 5,6-dihydro-2H-pyran-2-acetates involves a Prins cyclization of acrylyl enol ethers mediated by TMSOTf.This strategy was used in the total synthesis of the natural compound (+)-civet (13JOC12182). Highly functionalized tricyclic dihydropy-ranopyrrolidin-2-ones are formed by a catalytic P,Y-selective Diels-Alder [4 + 2] annulation of a,P-unsaturated y-butyrolactams, in good yields and enantioselectivities (Scheme 8) (13AGE11329). 

A reported diastereoselective synthesis of precursor A of vitamin D3 involved the use of 2-methylcyclopent-2-enone as starting material. The Mukaiyama-Michael conjugate addition of ketene acetal 269 in the presence of trityl hexachloroaniimonate afforded the adduct 270. The lateral chain was introduced, according the procedure of Tsuji, by the treatment of crude 270 with allyl carbonate and palladium dibenzylideneacetone " (Scheme 63). The expected product 271 was obtained in 63% yield from 269. Reduction of 271 with LAH afforded a mixture of diols that was selectively tosylated at the primary hydroxy group. The secondary hydroxy group was protected with the methoxymethyl group and further functional modifications afforded the lactone 272. The reaction of lithium dimethyl methylphosphonate with the lactone 272 completed the synthesis of the AB-des-cholestane derivative 273. 

Kluge M, Schneider B, Sicker D (1997) Diastereoselective synthesis of the benzoxazinone acetal ghnxrside ent-GDlMBOA The first enantiomer of a natural acetal ghicoside Carbohydrate Research 298 147 152... 

Sagar, R., Park, J., Koh, M., Park, S. B. (2009). Diastereoselective synthesis of polycyclic acetal-fused pyrano[3,2-c]pyran-5(2//)-one derivatives. Journal of Organic Chemistry, 74, 2171-2174. 

Sato, T., K. Tajima, and T. Fujisawa Diastereoselective synthesis of erythro- and threo-2-hydroxy-3-methyl-4-pentenoic acids by the ester enolate Claisen rearrangement of 2-butenyl 2-hydroxy acetate. Tetrahedron Letters 24, 729 (1983). 

We used two synthetic methods to access these chiral alcohols, the first one being a diastereoselective synthesis using a chiral acetal developed by Kagan et al. [42, 43], the second one being a resolution via separation of a diastereoisomeric mixture as developed by Weissensteiner et al. [44],... 

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

Hepatite Virus NS3/4A having the pyrrolidine-5,5-trans-lactam skeleton [83], starting from (R)- and (S)-methionine, respectively. The key step is the addition of the proper silyl ketene acetal to an iminium ion, e.g., that generated by treatment of the intermediate 177 with boron trifluoride, which provided the adduct 178 with better diastereoselectivity than other Lewis acids. Inhibitors of hepatitis C virus NS3/4A were efficiently prepared by a similar route from (S)-methionine [83]. The addition of indole to a chiral (z-amino iminium ion was a completely diastereoselective step in a reported synthesis of tilivalline, a natural molecule which displays strong cytotoxicity towards mouse leukemia L 1210 [84]. 

The threo stereoisomer was the major product obtained by the synthesis in Scheme 13.14. This stereochemistry was established by the conjugate addition in Step A, where a significant (4-6 1) diastereoselectivity was observed. The C(4)-C(7) stereochemical relationship was retained through the remainder of the synthesis. The other special features of this synthesis are in Steps B and C. The mercuric acetate-mediated cyclopropane ring opening was facilitated by the alkoxy substituent.19 The reduction by NaBH4 accomplished both demercuration and reduction of the aldehyde group. 

Moreover, a twofold SN -type domino reaction was reported by Krische and coworkers for the synthesis of y-butenolides 2-229 (Scheme 2.53) [128]. Treatment of Morita-Baylis-Hillman acetates 2-226 with trimethylsilyloxyfuran (2-227) in the presence of triphenylphosphane in THF at 0 °C led to 2-229 in yields of up to 94% and diastereoselectivities of >95 5. 

Notably, the Mukaiyama aldol/lactonizahon approach has been used in the total synthesis of panclicin D (2-258) [139b,c] and okinonellin B (2-261) (Scheme 2.61) [139d]. In the synthesis of 2-258, aldehyde 2-254 and the ketene acetal 2-255 were used to prepare the 3-lactone 2-256 with high simple and induced diastereoselectivity. There follows an esterification with the carboxylic acid 2-257. For the synthesis of 2-261, the aldehydes 2-259 and 2-252b were employed as substrates leading initially to the (1-lac tone 2-260. 

The simplest nitroalkene, nitroethene, undergoes Lewis acid-promoted [4+2] cycloaddition with chiral vinyl ethers to give cyclic nitronates with high diastereoselectivity. The resulting cyclic nitronates react with deficient alkenes to effect a face-selective [3+2] cycloaddition. A remote acetal center controls the stereochemistry of [3+2] cycloaddition. This strategy is applied to synthesis of the pyrrolizidine alkaloids (+)-macronecine and (+)-petasinecine (Scheme 8.33).165... 

Chiral acetals/ketals derived from either (R,R)- or (5,5 )-pentanediol have been shown to offer considerable advantages in the synthesis of secondary alcohols with high enantiomeric purity. The reaction of these acetals with a wide variety of carbon nucleophiles in the presence of a Lewis acid results in a highly diastereoselective cleavage of the acetal C-0 bond to give a /1-hydroxy ether, and the desired alcohols can then be obtained by subsequent degradation through simple oxidation elimination. Scheme 2-39 is an example in which H is used as a nucleophile.97... 

In the synthesis of D-eryt/zro-sphingosine (78 without BOC protection), the key step is the asymmetric aldol reaction of trimethylsilylpropynal 75 with ke-tene silyl acetal 76 derived from a-benzyloxy acetate. The reaction was carried out with 20 mol% of tin(II) triflate chiral diamine and tin(II) oxide. Slow addition of substrates to the catalyst in propionitrile furnishes the desired aldol adduct 77 with high diastereo- and enantioselectivity (syn/anti = 97 3, 91% ee for syn). In the synthesis of protected phytosphingosine (80, OH and NH2 protected as OAc and NHAc, respectively), the asymmetric aldol reaction is again employed as the key step. As depicted in Scheme 3-27, the reaction between acrolein and ketene silyl aectal 76 proceeds smoothly, affording the desired product 80 with 96% diastereoselectivity [syn/anti = 98 2) and 96% ee for syn (Scheme 3-27).50... 

---