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Applications of Alkyl Orthoesters As Valuable Substrates in Organic Transformations, Focusing on Cite This: RSC Adv., 2020, 10,30314 Reaction Media

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Applications of Alkyl Orthoesters As Valuable Substrates in Organic Transformations, Focusing on Cite This: RSC Adv., 2020, 10,30314 Reaction Media RSC Advances View Article Online REVIEW View Journal | View Issue Applications of alkyl orthoesters as valuable substrates in organic transformations, focusing on Cite this: RSC Adv., 2020, 10,30314 reaction media Zahra Khademi and Kobra Nikoofar * In this review we focus on applications of alkyl orthoesters as valuable and efficient substrates to perform various classes of two-component and multi-component organic reactions. The article has classified them according to two aspects, which are: (i) a focus on the reaction medium (solvent-free conditions, aqueous media, and organic solvents); and (ii) an examination of product structures. Reaction accomplishment under solvent-free conditions is an eco-friendly process with the absence of volatile toxic solvents, which puts it in Received 16th June 2020 line with green chemistry goals. Water is an interesting choice in organic transformations due to its Accepted 27th July 2020 inexpensiveness and safety. The authors hope their assessment will help chemists to attain new DOI: 10.1039/d0ra05276k approaches for utilizing alkyl orthoesters in various organic synthetic methods. The review covers the Creative Commons Attribution-NonCommercial 3.0 Unported Licence. rsc.li/rsc-advances corresponding literature up to the beginning of 2020. 1. Introduction (e) 3,3,3-Triethoxy-1-propyne (HCC(OEt)3, 8). Orthoesters may be considered to be products of the Orthoester (1,1,1-triorganyloxyalkane) (1) is the general name exhaustive alkylation of unstable orthocarboxylic acids and it is for a functional group containing three alkoxy groups attached from these that the name “orthoester” is derived. Orthoesters to one central carbon atom, with the general formula RC(OR')3. are highly reactive owing to the electron-de cient central In fact they are the esters of orthoacids which do not exist in carbon atom caused by the –Ieffect of the electronegative 1 This article is licensed under a a free state.1,2 Orthoesters were rst synthesized via nucleophilic groups OR. Among the ortheosters introduced above, TEOF the substitution reaction of chloroform (2) with alkoxides (3)by involved maximal exploitation in the reactions based on our Williamson and Kay in 1854 (Scheme 1).3 There are several literature survey (109 reports) followed by TMOF (54 reports), examples of acyclic alkylorthoesters such as:4 TEOAc (21 cases), TMOAc (4 items), and triethyl orthopropio- Open Access Article. Published on 17 August 2020. Downloaded 10/4/2021 5:58:11 AM. (a) Trimethyl orthoformate (TMOF) is the simplest nate (2 cases), and other kinds of alkyl orthoesters (1 case) orthoester in organic chemistry, which is also called trime- (Fig. 1a). Several orthoesters were applied in various domains as – – thoxymethane, 2-methoxyacetaldehyde dimethyl acetal, dehydrating agents,5 18 alkylating agents,19 24 dialkox- methoxymethylal, and methyl orthoformate. This colorless ymethylation agents,25 esterication agents,26 methoxy sour- – – – liquid with a pungent odor is soluble in ethanol and ether ces,27 additives,28 30 solvents,31 33 and protecting groups.34 36 This À1 ((CH(OMe)3, 4), bp ¼ 100.6 C, and d ¼ 0.9676 g mL ). functional group is also necessary for some conversions such as – 37 (b) Triethyl orthoformate (TEOF, CH(OEt)3, 5), also called the Johnson Claisen rearrangement. Fig. 1b demonstrates the diethoxymethoxyethane, triethoxymethane, and ethyl ortho- assorted applications mentioned vs. the type of orthoester. As formate a colorless volatile liquid with bp ¼ 146 C and d ¼ specied, TMOF and TEOF are the most commonly used in À 0.891 g mL 1, is the orthoester of formic acid. different processes, except for the case of rearrangements where (c) Triethyl orthoacetate (TEOAc, CH3C(OEt)3, 6) 1,1,1-trie- TMOAc is the most abundant. À thoxyethane, (bp ¼ 142 C, d ¼ 0.885 g mL 1), is an oily yellow to Different kind of orthoesters also have many applications in – colorless liquid with a pungent odor. several branches of science, such as polymers,38 43 liquid- 44 45–49 50–56 (d) Triethyl orthopropionate (CH3CH2C(OEt)3, 7), also called crystalline compounds, biochemistry, medicine and – 1,1,1-triethoxypropane and orthopropionic acid triethyl ester, is medicinal organic chemistry,57 60 inorganic chemistry,61,62 À a clear colorless liquid (bp ¼ 155–169 C, d ¼ 0.886 g mL 1) organometallic chemistry,63 dynamic covalent chemistry,64 – which is soluble in alcohol, chloroform, ethyl acetate, and ether supramolecular chemistry,65 68 and crystal structure analysis.69 and hydrolyzes slowly in water. Orthoesters have also been used in the synthesis of natural products, e.g. loganin is a monoterpene glucoside occupying a central position in the generation of secoiridoids and alka- Department of Chemistry, Faculty of Physics & Chemistry, Alzahra University, P.O. Box 1993891176, Tehran, Iran. E-mail: [email protected]; kobranikoofar@yahoo. loids, obtained from orthoesters biosynthetically. Because of com; Fax: +982188041344; Tel: +982188041344 this, in 1973, Buechi and co-workers described the total 30314 | RSC Adv.,2020,10,30314–30397 This journal is © The Royal Society of Chemistry 2020 View Article Online Review RSC Advances Scheme 1 The Pinner reaction for orthoester synthesis. Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Fig. 1 The abundances of different orthoesters as substrates in organic transformations (a), assorted applications of different kinds of orthoesters in some processes (b), and the classification of their utilization in various domains of science and technology (c). synthesis of loganin. It should be noted that trimethyl ortho- 1976, Greenlee and Woodward reported the total synthesis of This article is licensed under a formate was employed in some of the steps in the preparation of marasmic acid, one of the many fungal metabolites obtained loganin,70 and the total synthesis of (À)-monomorine,71 and from the Basidiomycetes, in which trialkyl orthoformates were (Æ)-vernolepin.72 It has been reported that TEOF is exploited in applied in some of the syntheses.74 Chan and Koide utilized 73 Open Access Article. Published on 17 August 2020. Downloaded 10/4/2021 5:58:11 AM. the total synthesis of palytoxin, as a marine natural product. In orthoesters for the rst total synthesis of the stresgenin B Scheme 2 The electrochemical synthesis of highly fluorinated orthoesters. This journal is © The Royal Society of Chemistry 2020 RSC Adv.,2020,10,30314–30397 | 30315 View Article Online RSC Advances Review Scheme 3 A synthetic approach to 2,6,7-trioxabicyclo[2.2.2]octane orthoesters. scaffold as a heat shock protein expression inhibitor.75 The Gauthier and Deslongchamps obtained twistane via a multi- application of orthoesters in the synthesis of condensed carbon- step process started by TEOF as one of the substrates.76 The cage organics was investigated in the preparation of twistane as diagram in Fig. 1c illustrates the vast range of applications of a cycloalkane and also the simplest diamondoid. In 1967, different kinds of orthoesters in various sciences. The results Creative Commons Attribution-NonCommercial 3.0 Unported Licence. This article is licensed under a Scheme 4 The preparation of 2,4-di-O-benzoyl-myo-inositol 1,3,5-orthoformate. Open Access Article. Published on 17 August 2020. Downloaded 10/4/2021 5:58:11 AM. Scheme 5 The synthesis of spiro orthoesters. 30316 | RSC Adv.,2020,10,30314–30397 This journal is © The Royal Society of Chemistry 2020 View Article Online Review RSC Advances Scheme 6 The Rh(II)-catalyzed synthesis of spirocyclic orthoesters. indicate the comprehensive use of orthoesters in many domains presence of N,N-diisopropylethylamine or 1,8-diazabicyclo- of science and technology. [5.4.0]undec-7-ene (DIPEA/DBU) as basic electrolytes by boron- In addition to the Williamson and Kay method, there are doped diamond (BDD) electrodes under a constant current À À various procedures for the preparation of orthoesters. The density of 7.2 mA cm 2 until a catalytic quantity of 3.0 F mol 1 Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Pinner reaction of nitriles (9) with alcohols (10) in the presence of electricity has passed (Scheme 2).82 of strong acids generated orthoesters (Scheme 1).77 Electro- Secondary and tertiary amides (15) were reacted with triic 78–81 chemical approaches are also employed for the synthesis of anhydride (16) by pyridine in CH2Cl2 at low temperatures to these compounds, e.g., new highly uorinated orthoesters (14) form imino and iminium triates within 4 h, which on treat- were synthesized through the functionalization of 1,3-benzo- ment with 2,2-bishydroxymethyl-1-propanol (17) utilizing pyri- dioxoles (11) in the 2 position with diverse uorinated alcohols dine buffered solution attained 2,6,7-trioxabicyclo[2.2.2]octane (such as 1,1,1,3,3,3-hexauoropropan-2-ol (HFIP, 12) or 2,2,2- orthoesters (18) (Scheme 3).83 triuoroethanol (TFE, 13)) in an undivided cell and in the This article is licensed under a Open Access Article. Published on 17 August 2020. Downloaded 10/4/2021 5:58:11 AM. Scheme 7 Synthetic procedure for peracetylated orthoester. This journal is © The Royal Society of Chemistry 2020 RSC Adv.,2020,10,30314–30397 | 30317 View Article Online RSC Advances Review Tetrahydropyranyl acetals containing a phenyl diazoketone substituent (24) underwent Rh(II)-catalyzed C–H insertion through an unusual C–O bond generation to give spirocyclic orthoesters (25) (Scheme 6).86 3,4,6-Tri-O-acetyl-1,2-O-(1-tocopheroxyethylidene)-a-D-gluco- pyranose (vitamin E sugar 1,2-orthoester) (33–36) with exo-type stereoselectivity were synthesized through the reaction of sugar halides (26–29) with various phenols, such as a-tocopherol (30), Scheme 8 The synthesis of orthoesters via the methoxylation of cyclic chroman-6-ol (31), and 2,6-dimethylphenol (32)byN,N-diiso- acetals.
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