Alkoxyacrylate

There have heen many studies on the polymerizability of a-substituted acrylic monomers.3jU35 33S It is established that the ceiling temperature for a-alkoxyacrylates decreases with the size of the alkoxy group. 35 However, it is of interest that polymerizations of a-(alkoxymethyl)acrylates (67)3 15 and a-(acyloxymethyl)acrylates (68)and captodative substituted monomers (69, 70) 39 appear to have much higher ceiling temperatures than the corresponding a-alkylacrylates methyl ethacrylate, MEA). For example, methyl a-... 

As a strategy for the construction of cyclic ethers, the radical cyclization of jS-alkoxyacrylates was used for the preparation of czs-2,5-disubstituted tetrahy-drofurans and cis-2,6-disubstituted tetrahydropyrans. An example is given with S-alkoxymethacrylate 38 as precursor of the optically active benzyl ether of (+)-methyl nonactate, exclusively formed as the threo product (Reaction 44). ° ... 

A novel polymerized vesicular system for controlled release, which contains a cyclic a-alkoxyacrylate as the polymerizable group on the amphiphilic structure, has been developed. These lipids can be easily polymerized through a free radical process. It has been shown that polymerization improves the stabilities of the synthetic vesicles. In the aqueous system the cyclic acrylate group, which connects the polymerized chain and the amphiphilic structure, can be slowly hydrolyzed to separate the polymer chain and the vesicular system and generate a water-soluble biodegradable polymer. Furthermore, in order to retain the fluidity and to prepare the polymerized vesicles directly from prev lymerized lipids, a hydrophilic spacer has been introduced. 

In related work, Rutjes and co-workers reported a four-step protocol from conveniently protected sugar derivatives to substituted C-l glycals (Scheme 16).77 The key step in their synthetic route included RCM of highly functionalized a-alkoxyacrylates. The potential of these glycal derivatives was illustrated by their conversion to natural products such as DAH (3-deoxy-D-arabino-2-heptulosonic acid) or KDO (3-deoxy-D-manno-2-ulosonic acid). 

Scheme 16 Ring-closing metathesis of carbohydrate-derived a-alkoxyacrylates. 

In contrast with olefins, alkoxy-alkoxycarbonylation of alkynes to give /J-alkoxyacrylic esters is not a common reaction, and has occasionally been observed as a side reaction of the main reaction pathway leading to maleates and fumarates [77,80]. However, with suitably functionalized alkynes bearing a coordinating group (such as o ,a -disubstituted propargylic acetates) it may become the major reaction course (Scheme 15) [88]. 

The configuration of the newly formed stereogenic center can be explained conceptually by a chair-like reactive conformation for radical 18. The (J-alkoxyacrylates utilized here by Lee prove to be extraordinarily effective radical acceptors.7... 

Boron tnchlonde acting as a Lewis acid cleaves ben/ylic ether 37 selectively to 38.IJ The third reaction, like the transiormation of 4 to 5, leads to a rranv-P-alkoxyacrylate 7... 

The intramolecular, radical-mediated cyclization of oj-halo-/ -alkoxyacrylates (formed from propiolates and >-halo alcohols) gives nearly quantitative yields of THF and tetrahy-dropyran ring systems (equation 184)660. The reaction is performed in refluxing benzene in the presence of BusSnH and AIBN. The functionalization in the 2-positions allows for further structural elaboration. Other similar radical cyclizations have also been performed as the key step in natural product synthesis661-663. 

The highly stereoselective synthesis of 2,3-fr,ms--3-hydroxytetrahydropyran and 2,3-/ra r-3-hydroxyoxepane was achieved by the Sml2-induced reductive intramolecular cyclization from acyclic compounds having an aldehyde and a /3-alkoxyacrylate fragments <2002CL148>. Based on this reaction, new effective iterative syntheses of trans-fused 6,6,6-tricyclic, 6,7,6-tricyclic, and 6,7,7,6-tetracyclic ethers were developed <2002T1853>. 

Examples of fused pyrans which can be obtained in a similar manner include 6-oxasteroids (95JCS(P1)1089) and bicyclic vinyl ethers (95CC1117), whilst a double radical cyclisation of 3-alkoxyacrylates features in a synthesis of 3Z-dactomelyne (95JA8017). 

Macralstonine, C44H54N4O5, crystallizes as colorless, rectangular rods, mp 293° (dec.), [a]D +27.5°, and contains one methoxyl, at least two C-methyl, and three, or possibly four, methylimino groups (33, 36). Its IR-spectrum discloses the presence of an imino or hydroxyl group, an alkoxyacrylic ester chromophore (peaks at 1652 and 1628 cm-1), and an o-disubstituted benzene nucleus. The formation of a derivative with dinitrophenylhydrazine indicates the presence of a potential carbonyl function. Macralstonine has also been reported to possess a marked hypotensive activity (36). 

Acyclic ethers having an aldehyde and a /3-alkoxyacrylate group undergo Sml2-induced reductive cyclization to afford oxocanes or oxocenes in moderate yield but with low stereoselectivity (Scheme 16) <2002CL148>. 

Use of aldehyde substrates for radical cyclization of y5-alkoxyacrylates presents opportunities for construction of fused oxacyclic systems. Under the tributylstan-... 

Scheme 23. Fused oxacyclic systems via radical cyclization of jff-alkoxyacrylates...

Acyl radical cyclization of ) -alkoxyacrylates provides five-, six-, and seven-mem bered oxacyclic ketones with high stereoselectivity [45], In a key step in the synthesis of (—)-kumausallene (55) by Evans, the tetrahydrofuran-3-one 69 was obtained stereoselectively from the acyl selenide 68 [46] (Scheme 24). 

There are a number of examples of 6-endo radical cyclization of vinylic ether substrates. For example, Thomas reported synthesis of the tetrahydropyran fragment 76 of bryostatin 1 via radical cyclization reaction of the a-alkoxyacrylate 75, capitalizing on the higher activity of Z-vinyl radicals [51] (Scheme 27). In the syn-... 

---