Carbonyl compounds acyclic

A carbonyl group can be protected as a sulfur derivative—for example, a dithio acetal or ketal, 1,3-dithiane, or 1,3-dithiolane—by reaction of the carbonyl compound in the presence of an acid catalyst with a thiol or dithiol. The derivatives are in general cleaved by reaction with Hg(II) salts or oxidation acidic hydrolysis is unsatisfactory. The acyclic derivatives are formed and hydrolyzed much more readily than their cyclic counterparts. Representative examples of formation and cleavage are shown below. 

Acyclic monothio acetals and ketals can be prepared directly from a carbonyl compound or by transketalization, a reaction that does not involve a free carbonyl group, from a 1,3-dithiane or 1,3-dithiolane. They are cleaved by acidic hydrolysis or Hg(II) salts. 

In the transition state, the torsional strain involving the partially formed bond between the nucleophile and the carbonyl group represents a substantial fraction of the total strain, even when the degree of bonding is low. Thus, in the case of acyclic carbonyl compounds, a staggered conformation is preferred in the transition state (Figure 6). 

Formation of C-C Bonds by Addition to Chiral Acyclic Carbonyl Compounds 1.3.1.3.1. Addition to Acyclic a-Alkyl-Substituted Carbonyl Compounds Cram-Selective 1,2-Asymmetric Induction... 

The Mukaiyama aldol reaction can provide access to a variety of (3-hydroxy carbonyl compounds and use of acetals as reactants can provide (3-alkoxy derivatives. The issues of stereoselectivity are the same as those in the aldol addition reaction, but the tendency toward acyclic rather than cyclic TSs reduces the influence of the E- or Z-configuration of the enolate equivalent on the stereoselectivity. 

Although the allylation reaction is formally analogous to the addition of allylic boranes to carbonyl derivatives, it does not normally occur through a cyclic TS. This is because, in contrast to the boranes, the silicon in allylic silanes has little Lewis acid character and does not coordinate at the carbonyl oxygen. The stereochemistry of addition of allylic silanes to carbonyl compounds is consistent with an acyclic TS. The -stereoisomer of 2-butenyl(trimethyl)silane gives nearly exclusively the product in... 

I. Condensation of N-Monosubstituted Hydroxylamines with Carbonyl Compounds Condensation of N -monosubstituted hydroxylamines with carbonyl compounds is used as a direct synthesis of many acyclic nitrones. The synthesis of hydroxylamines is being carried out in situ via reduction of nitro compounds with zinc powder in the presence of weak acids (NH4CI or AcOH) (14, 18, 132). The reaction kinetics of benzaldehyde with phenylhydroxylamine and the subsequent reaction sequence are shown in Scheme 2.21 (133). 

According to the first process, acyclic alkyl nitronates (73) afford corresponding oximes and carbonyl compounds (3) (Eq.l). This process is similar to the well-known Cope rearrangement (Eq.l ) (233). 

Davis et al.111 developed another method for reagent-controlled asymmetric oxidation of enolates to a-hydroxy carbonyl compounds using (+)-camphor-sulfonyl oxaziridine (147) as the oxidant. This method afforded synthetically useful ee (60-95%) for most carbonyl compounds such as acyclic keto esters, amides, and a-oxo ester enolates (Table 4-20). 

The reactions of allylmetal reagents with carbonyl compounds and imines have been extensively investigated during the last two decades [1], These carbon—carbon bondforming reactions possess an important potential for controlling the stereochemistry in acyclic systems. Allylmetal reagents react with aldehydes and ketones to afford homo-allylic alcohols (Scheme 13.1), which are valuable synthetic intermediates. In particular, the reaction offers a complementary approach to the stereocontrolled aldol process, since the newly formed alkenes may be readily transformed into aldehydes and the operation repeated. 

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],... 

In our laboratories, we have found that PdI2, in conjunction with an excess of iodide anions, constitutes an exceptionally efficient, selective and versatile catalyst for promoting a variety of oxidative carbonylation processes, leading to important acyclic as well as heterocylic carbonyl compounds. 

Reduction of conjugated carbonyl compounds using stoichiometric amounts of the ammonium salt shows little advantage over the sodium salt in acidic methanol [11] with both reagents producing allylic alcohols (58-88% for acyclic compounds and 15-64% for cyclic compounds) by selective 1,2-reduction of the conjugated systems. Aldehydes, ketones and conjugated enones are also reduced by tetra-n-butylammonium cyanoborohydride in HMPA [11, 12], whereas haloalkanes and alkanesulphonic esters are cleaved reductively under similar conditions [13]. 

Rate constants and Arrhenius parameters for the reaction of Et3Si radicals with various carbonyl compounds are available. Some data are collected in Table 5.2 [49]. The ease of addition of EtsSi radicals was found to decrease in the order 1,4-benzoquinone > cyclic diaryl ketones, benzaldehyde, benzil, perfluoro propionic anhydride > benzophenone alkyl aryl ketone, alkyl aldehyde > oxalate > benzoate, trifluoroacetate, anhydride > cyclic dialkyl ketone > acyclic dialkyl ketone > formate > acetate [49,50]. This order of reactivity was rationalized in terms of bond energy differences, stabilization of the radical formed, polar effects, and steric factors. Thus, a phenyl or acyl group adjacent to the carbonyl will stabilize the radical adduct whereas a perfluoroalkyl or acyloxy group next to the carbonyl moiety will enhance the contribution given by the canonical structure with a charge separation to the transition state (Equation 5.24). 

Further, the two forms can also equilibrate via the open-chain carbonyl form of the sugar, so that the single isomers in solution are rapidly transformed into the equilibrium mixture (see Box 7.1). Since there are two anomeric forms, and these are often in equilibrium via the acyclic carbonyl compound. 

The introduction of umpoled synthons 177 into aldehydes or prochiral ketones leads to the formation of a new stereogenic center. In contrast to the pendant of a-bromo-a-lithio alkenes, an efficient chiral a-lithiated vinyl ether has not been developed so far. Nevertheless, substantial diastereoselectivity is observed in the addition of lithiated vinyl ethers to several chiral carbonyl compounds, in particular cyclic ketones. In these cases, stereocontrol is exhibited by the chirality of the aldehyde or ketone in the sense of substrate-induced stereoselectivity. This is illustrated by the reaction of 1-methoxy-l-lithio ethene 56 with estrone methyl ether, which is attacked by the nucleophilic carbenoid exclusively from the a-face —the typical stereochemical outcome of the nucleophilic addition to H-ketosteroids . Representative examples of various acyclic and cyclic a-lithiated vinyl ethers, generated by deprotonation, and their reactions with electrophiles are given in Table 6. 

For the synthesis of nonannulated 2-amino-4H-pyrans, acyclic carbonyl compounds 24 are used in Methods 1,2, and 3. Generally, readily accessible ketones 24, as well as unsaturated nitriles 25 contain electron-withdrawing substituents (R, X). Consequently, densely functionalized pyrans 22 are formed. UNs, widely used for aminopyran preparation, include 30-34... 

The stereochemistry of addition of organometallic reagents to acyclic carbonyl compounds parallels the behavior of the hydride reducing agents, as discussed in Section... 

Aside from the relatively trivial conversions of nitronates to the corresponding oxime and carbonyl compounds (10,11), the chemistry of nitronates remained relatively unexplored for much of the early 1900s. However, in 1964, Tartakovskii et al. (12) demonstrated that alkyl nitronate esters were competent partners in the newly discovered class of dipolar cycloadditions with alkenes (Scheme 2.1). Both cyclic and acyclic nitronates participated, thus providing a new functional group were the nitrogen atom existed at the center of an acetal (13). These compounds were subsequently referred to as nitroso acetals (14) or nitrosals (15). 

A great deal of the interest in isoxazolines stems from their use in the synthesis of acyclic compounds (19). The approach to (3-hydroxy carbonyl compounds via... 

Saito et al. (32,121) developed a variety of tartaric acid derivatives, including Ci-symmetric chiral alkenes such as 76. The 1,3-dipolar cycloaddition between 76 and 77 gave primarily endo-1%. (Scheme 12.26) The diastereofacial selectivity of the reaction is excellent, as endo-1% is obtained with >98% de. Other cyclic and acyclic nitrones have been employed in reactions with 76, and in all cases, moderate to excellent endo/exo-selectivities and excellent diastereofacial selectiv-ities were obtained (32,121). Three other research groups have applied various y-hydroxylated ot,p-unsaturated carbonyl compounds in related reactions with nitrones (122-124). However, the selectivities were somewhat lower than those obtained by Saito and et al. (32,121). 

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