Bromomethyl Acrylate

Rautenstrauch, V Helv Chim Ada 1974, 57, 496, Ohno, A, Yamabe, T, Nagata, S Bull Chem So Jpii 1975, 48, 3718 

Chemical Abstracts Nomenclature (Collective Index Number) (Registry Number) 

METHYL ot-(BROMOMETHYL)ACRYLATE (2-Propenoic acid, 2-(bromomethyl)-, methyl ester) 

Submitted by John M Cassady, Gary A Howie, J Michael Robinson, and lOANNis K Stamos  

Checked by Paul R West and Orvili f I Chapman 1. Procedure 

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Reaction of 2,3-dihydro-3-hydroxy-3-methyl- 240 (R = Me), or a mixture of 2,3-dihydro-3-hydroxy-3-aryl-57/-pyrido[l,2,3-dfe]-l,4-benzoxazin-5-ones 240 (R = Ar) and (8-aroylmethoxy)quinolin-2(l//)-ones 241 (R = Ar) with ethyl 2-(bromomethyl)acrylate in the presence of activated Zn and hydroquinone gave 8-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-furanyl)-methoxy]quinolin-2(l//)-ones (242) (97HCA1161). 6,7-Dihydro derivatives of 240 reacted similarly (00HCA349). 

These reagents exhibit a high selectivity for the attack of aldehydic over ketonic oxo groups26. The triethylammonium salt of 2-(bromomethyl)acrylic acid and base-sensitive aldehydes, under these conditions, can be used for the synthesis of lactones27. 

Recently, optically active (+)-(R)-methy 1 tolyl sulfoxide 102, R = H was alkylated with a very high diastereoselectivity136. The sulfoxide was treated with either lithium diisopropy-lamide (LDA) or lithium tetramethylpiperidide (LTMP) to form the lithio-derivative, which upon subsequent reaction with lithium a-bromomethyl acrylate gave a mixture of two diastereomers of a-methylene-y-sulfinylcarboxylic acid 103. The use of the sterically highly hindered base, LTMP, gave the product with a higher diastereoselectivity. For example, the Sc4 Rc4 ratio was 95 5 when R was the methyl group. 

In 1991, Li and Chan reported the use of indium to mediate Barbier-Grignard-type reactions in water (Eq. 8.49).108 When the allylation was mediated by indium in water, the reaction went smoothly at room temperature without any promoter, whereas the use of zinc and tin usually requires acid catalysis, heat, or sonication. The mildness of the reaction conditions makes it possible to use the indium method to allylate a methyl ketone in the presence of an acid-sensitive acetal functional group (Eq. 8.50). Furthermore, the coupling of ethyl 2-(bromomethyl)acrylate with carbonyl compounds proceeds equally well under the same reaction conditions, giving ready access to various hydroxyl acids including, for example, sialic acids. 

Improvement to the Reformatsky reactions was achieved (53) by the use of a highly activated zinc - silver couple dispersed on the surface of graphite. T reatment of protected aldono-1,4-lactones 10b or 25b and 1,5-lactones 51a or 51b with a Reformatsky reagent prepared from a-haloesters or alkyl 2-(bromomethyl)acrylates resulted in the formation of the corresponding 3-or 4-glyculofuranos (or pyranos)onates 49a,b-50a,b, or 52a,b, respectively, under mild conditions (— 40 ° to 00) and in very good yields. Ethyl 2-deoxy-2-fluoro (and 2-bromo)-a-D-wa o-3,6-furanos-3-octulosonate derivatives were also obtained. 

The four components required for the key Ugi reaction are simple aldehydes and amines such as isopropylamine and isobutyraldehyde, isonitrile 85 and a-(bromomethyl)acrylic acid and derivatives (86). Isonitrile 85 was synthesized from tyrosamine in three straightforward steps [94]. 

Ethyl a-(bromomethyl)acrylate Acrylic acid, 2- bromomethyl)-, ethyl ester (8) 2-Propenoic acid, 2-(bromomethyl)-, ethyl ester (9) (17435-72-2)... 

Ethyl a-(hydroxyraethyl)acrylate can be used for the synthesis of chloro and bromomethyl acrylates. The fluoro and iodo compounds have been prepared easily by halogen exchange from ethyl a-(bromomethyl)acrylate, ... 

The procedure described here is relatively new and gives improved overall yields of 60-67% for the preparation of ethyl a-(bromomethyl)acrylate in two stages from commercially available starting materials. Other more complex and less productive procedures have been described. ... 

Ethyl a-(bromomethyl)acrylate has been used extensively for the synthesis... 

Ethyl oL-(hydroxymethyl)acrylate.3 This useful acrylate (2) can be prepared in —75% yield by reaction of triethyl phosphonoacetate with a 30% aqueous solution of formaldehyde. It is converted to ethyl a-(bromomethyl)acrylate by reaction with PBr3 in ether (—85% yield). 

Ethyl 3,3-bi s(trIfluoromethyl)-propenoate, AJ6T Ethyl bromide, AA80 Ethyl bromoacetate, AC93 Ethyl 4-bromobutanoate, AH83 Ethyl bromoethanoate, AC93 Ethyl (bromomethyl)acrylate, AH56 Ethyl 2-(bromomethyl)propenoate, AH56... 

Bicyclic keto esters can easily be prepared by a process called a,a -annulation.29 Thus, treatment of the enamine of cyclopentanone (64) with ethyl a-(bromomethyl)acrylate (98) affords, after work-up, the bicyclic keto ester (99) in 80% yield (equation IS).2911 The mechanism probably involves an initial Michael addition and elimination (or a simple Sn2 or Sn2 alkylation) followed by an intramolecular Michael addition of the less-substituted enamine on the acrylate unit. The use of the enamine of 4,4-bis(ethoxycarbonyl)cyclohexanone (100 equation 26) with (98) gives a 45% yield of the adaman-tanedione diester (101) (yield based on 100 70% when based on 98) via a,a -annulation followed by Dieckmann condensation.29 Enamines of heterocyclic ketones can also serve as the initial nucleophiles, e.g. (102) and (103) give (105) via (104), formed in situ, in 70% yield (Scheme 11 ).29>... 

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