Orthoesters reaction with alcohols

All the foregoing syntheses of 0,0,0-orthoesters required at least two steps because 0,0,0-orthoesters cannot usually be prepared directly from esters by reaction with alcohols under add conditions analogous to the preparation of acetals from aldehydes and ketones. There are some exceptions.237 -239 For example. reaction of the racemic mixture of cis- and fraftf-lactones in Scheme 2.115 with (/ ,/ )-butane-2,3-diol in refluxing benzene afforded a mixture of four diastereoisomeric orthoesters (99%) in the ratio 6 6 1 1 that could be sepa-... 

The ring-opening process of Equation 8.45 is, of course, simply the reverse of the process by which oxiranes (oxacyclopropanes, epoxides) are formed from halohy-drins (e.g., see item 3,Table 7.6). Further, as written, the processes shown in Schemes 8.90-8.92 are reversible and thus, at least in principle, carbonyl compounds can be converted to enol ethers, acetals (and ketals), and orthoesters. However, while acetals and ketals readily form from alcohols and acids under dehydrating conditions (Chapter 9) and esters undergo exchange reactions with alcohols in the... 

A. Claisen Rerrangements of Ketene Aminats and Imidates. A reaction that is related to the orthoester Claisen rearrangement utilizes an amide acetal, such as dimethylacetamide dimethyl acetal, in the exchange reaction with allylic alcohols.257 The products are y, 8-unsaturated amides. The stereochemistry of the reaction is analogous to the other variants of the Claisen rearrangement.258... 

Insertion of a ketocarbene moiety into a C—O bond of orthoesters is normally performed with catalysis by BF3 Et20. Copper(II) trifiouromethanesulfonate was found to be a similarly efficient catalyst also, at least in some cases, whereas Rh2(OAc)4 was much less suited to promote this transformation l60). Besides the C/O insertion product 343, the alcohol insertion product 344 and, in reactions with ethyl diazoacetate, the formal carbene dimers were obtained. In agreement with BF3 EtzO, Cu(OTf)2 did not bring about insertion into a C—O bond of trimethyl... 

In 1964, Kochetkov, Khorlin and Bochkov reported that the reaction of 1,2-alky-lorthoacetates with alcohols in the presence of catalytic amounts of HgBr2 and pTsOH furnished acetylated 1,2-trans glycosides or isomeric orthoesters depending on the reaction conditions [4]. Polar solvents (nitromethane, acetonitrile) and large amounts of catalyst promoted glycosylation (a, Scheme 5.5), whereas solvents of low polarity (dichloroethane) and the use of small amounts of catalyst favored transorthoesterification (b, Scheme 5.5) [16]. 

In contrast to Mori s synthesis, Pawar and Chattapadhyay used enzymatically controlled enantiomeric separation as the final step [300]. Butanone H was converted into 3-methylpent-l-en-3-ol I. Reaction with trimethyl orthoacetate and subsequent Claisen-orthoester rearrangement yielded ethyl (E)-5-methyl-hept-4-enoate K. Transformation of K into the aldehyde L, followed by reaction with ethylmagnesium bromide furnished racemic ( )-7-methylnon-6-ene-3-ol M. Its enzyme-catalysed enantioselective transesterification using vinylacetate and lipase from Penicillium or Pseudomonas directly afforded 157, while its enantiomer was obtained from the separated alcohol by standard acetylation. 

Orthoesters of polynitroaliphatic alcohols have been synthesized in the presence of metal chloride Lewis acid catalysts. Tetrakis(2,2,2-trinitroethyl)orthocarbonate (180) and tris(2,2,2-trinitroethyl)orthoformate (181) are obtained from the reaction of 2,2,2-trinitroethanol (159) with carbon tetrachloride and chloroform, respectively, in the presence of anhydrous ferric chloride.333729 Analogous reactions with 2-fluoro-2,2-dinitroethanol have been reported.3 ... 

Carboxylic acids can also be protected as ortho esters. Ortho esters derived from simple alcohols are very easily hydrolyzed, and a more useful ortho ester protecting group is the 4-methyl-2,6,7-trioxabicyclo[2.2.2]octane structure. These bicyclic orthoesters can be prepared by exchange with other ortho esters, by reaction with iminoethers, or by rearrangement of the ester derived from 3-hydroxymethyl-3-methyloxetane. 

A second method is based on the abnormal course of the Koenigs-Knorr reaction with fluoroalkyl alcohols. Indeed, when there are two or three methylenes between the Rf group and the hydroxyl, the reaction does not lead to substitution of the anomeric bromide but instead affords an orthoester. In the presence of mercuric bromide, this orthoester can undergo a rearrangement into an (9-fluoroalkyl glycoside (Figure 6.47). 

Selective reaction of the bromochloro compound 83 with silver fluoride in acetonitrile gave a good yield of the product of nucleophilic displacement of bromide with inversion of configuration, namely, 151, and treatment with an excess of the reagent afforded25 the g m-difluoride (152). With alcohols in the presence of silver triflate, compound 83 affords access to orthoesters (for example, the dimethyl compound 153), and with diols sp/ro-analogs (for example, 154, which has the orthoester structural feature of the orthosomy-cins), are obtained.88... 

Alkoxy-l,3-dioxoles are best prepared using the Diels-Alder methods discussed in Section 4.30.3.2.3. The corresponding 1,3-oxathioles are not well known, but have been reported from the reaction of l-(acylthio)-l-alkynes with alcohols (74RTC99), as shown in equation (49). 1,3-Dioxolanes and 1,3-oxathiolanes containing a 2-alkoxy substituent are easily prepared using an orthoester and a glycol or 2-mercaptoalcohol. 

Acid Catalyst. Camphorsulfonic acid (CS A) has been used extensively in synthetic organic chemistry as an acid catalyst. It has particularly been used in protecting group chemistry. For example, hydroxyl groups can be protected as tetrahydropyranyl (THP) ethers using dihydropyran and a catalytic amount of CSA (eq 1). Both 1,2- and 1,3-diols can be selectively protected by reaction with orthoesters in the presence of camphorsulfonic acid to form the corresponding cyclic orthoester (eq 2) This method of protection is particularly useful in that reduction of the orthoester with Diisobutylaluminum Hydride forms the monoacetal, which allows for preferential protection of a secondary alcohol in the presence of a primary alcohol. Ketones have also been protected using catalytic CSA (eq 3). ... 

While the chlorides of strongly electropositive elements such as thorium, lanthanides, and some later 3d metals form adducts with alcohols (57), anhydrous chlorides of boron (6) and silicon (9) form the corresponding alkoxides or alkyl orthoesters, B(OR)3 and Si(OR)4, with primary and secondary alcohols. The reactions of tertiary alcohols are complicated by the facile side formation of tertiary alkyl chloride and water by the reaction between tertiary alcohols... 

The most straightforward synthesis of acyclic carbonates from C02 is its dehy-drative condensation with alcohols (Scheme 6.7). This reaction is catalyzed by a variety of soluble and solid catalysts, with organometallic Sn derivatives such as Bu2Sn(OMe)2 playing a significant role. Typical reaction conditions include 140-180°C and up to 300 bar C02 pressure. A particular problem is that water accumulation affects unfavorably the chemical equilibrium furthermore, it acts as a catalyst poison and therefore it must be removed from the reaction mixture. Orthoesters (e.g., trimethyl orthoacetate) and acetals (e.g., dimethyl acetal) that work as internal water scavengers can be used as starting materials instead of the... 

The alcohol 470 was prepared from the mesylate 469 by reaction with diethyl malonate followed by reduction to give 470, whose selective acetylation was carried out by reaction with trimethyl orthoacetate followed by acid hydrolysis of the cyclic orthoester intermediate. Bromination and then coupling gave 471 [88JCS(P1)2757]. 

This reaction was first reported by Johnson et al. in 1970. It is a highly stereoselective synthesis of y,5-unsaturated esters from the reaction between allylic alcohols and an orthoester in the presence of a trace amount of weak acid, such as propionic acid. Because this reaction is the modification or variant of the Claisen Rearrangement, it is often referred to as the Johnson orthoester Claisen rearrangement. Occasionally, this reaction is also known as the Claisen-Johnson orthoester rearrangement, " or Johnson orthoester protocol. This reaction involves the formation of mixed orthoester from allyl alcohol and the added orthoester, which loses an alcoholic component to form a ketene acetal then migrates to unsaturated carbonyl compounds via the Claisen Rearmagement with high syn selectivity. Posner further extended this reaction to use sulfonyl orthoester. Overall, this reaction has been applied to the synthesis of a variety of complicated natural products, such as squalenes. ... 

D-Glucose orthoesters of complex alcohols can be easily obtained with the help of silver salicylate Alcohols and amines can be conveniently prepared from olefins by ozonization-reduction and ozoni-zation-reductive amination respectively without isolation of intermediates Inverted amines can be obtained from optically-active alcohols through stereospecific formation of N-alkylphthalimides 3-Methoxy-l-phenyl-l-propyne has been used as starting material for the synthesis of a,/ -unsatd. carbonyl compounds through allenic di-carbanions a-Ketocarboxylic acids can be easily prepared from cyanohydrins through a Ritter reaction... 

In connection with structure activity relationship studies, Chapuis [40] prepared a series of sandalwood odorant alcohols. In this context, alcohol 181 has been prepared from (+)-trans-pinocarveol 179 in two steps. Accordingly, orthoester rearrangement of alcohol 179 afforded ester 180 which, after the Grignard reaction, gave tertiary alcohol 181 (Scheme 6.27). 

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