Reaction of 1,3-Thiazole-5(4H)-thiones with 1,2-Epoxycycloalkanes: Formation of Spirocyclic 1,3-Oxathiolanes

2013

Helvetica Chimica Acta

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Addition reactions of acid chlorides with various 2-substituted 4,5-dihydro-4,4-dimethyl-5-(methylsulfanyl)-1,3-thiazoles under basic conditions were studied. Two kinds of products were obtained from these additions, beta-lactams and non-beta-lactam adducts. When the reaction was carried out with 4,5-dihydro-1,3-thiazoles with a Ph substituent at C(2), the reaction proceeded via formal [2+2] cycloaddition and led to the correspoding beta-lactam. On the other hand, acid chlorides and 4,5-dihydro-1,3-thiazoles bearing an alpha-H-atom at the C(2)-substituent underwent C(alpha)-and/or N-addition reactions and furnished non-beta-lactam adducts, i.e., C(alpha)-and/or N-acylated 1,3-thiazolidines. The attempted transformations of sulfonyl esters of exo-6-hydroxy penams to endo-6-azido penams failed, although they were successful with mono-beta-lactams under the same conditions.

mentioning

confidence: 67%

Reactions of Acid Chlorides/Ketenes with 2‐Substituted 4,5‐Dihydro‐4,4‐dimethyl‐1,3‐thiazoles: Formation of Penam Derivatives

Shi

2013

Helvetica Chimica Acta

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“…The observed inversion of the configuration of one oxirane Catom indicates an S n 2-type mechanism, involving an attack of the oxo compound onto the activated oxirane. For the reaction between thiocarbonyl compounds and oxiranes under similar conditions, we have proposed an analogous mechanism in our previous work [1] [2] (cf. also [6] [7]) (Scheme 1).…”

Section: Introduction ± the Reaction Of Oxo Compounds With Oxiranes mentioning

confidence: 99%

Stereochemical Course of the Reaction between Thiocarbonyl Compounds and Oxiranes: Reaction withcis- andtrans-2,3-Dimethyloxirane

Blagoev

2000

HCA

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The reactions of thiocarbonyl compounds with cis-2,3-dimethyloxirane (1a) in CH 2 Cl 2 in the presence of BF 3´E t 2 O or SnCl 4 led to trans-4,5-dimethyl-1,3-oxathiolanes, whereas with trans-2,3-dimethyloxirane (1b) cis-4,5-dimethyl-1,3-oxathiolanes were formed. With the stronger Lewis acid SnCl 4 , the formation of side-products was also observed. In the case of 1,3-thiazole-5(4H)-thione 2, these side-products are the corresponding 1,3-thiazol-5(4H)-one 5 and the 1 : 2 adduct 8 (Schemes 2 ± 4). Their formation can be rationalized by the decomposition of the initially formed spirocyclic 1,3-oxathiolane and by a second addition onto the CN bond of the 1 : 1 adduct, respectively. The secondary epimerization by inversion of the configuration of the spiro-Catom (Schemes 5 ± 7) can be explained by a Lewis-acid-catalyzed ring opening of the 1,3-oxathiolane ring and subsequent ring closure to the thermodynamically more stable isomer (Scheme 12). In the case of 2,2,4,4-tetramethyl-3-thioxocyclobutanone (20), apart from the expected spirocyclic 1,3-oxathiolanes 21 and 23, dispirocyclic 1 : 2 adducts were formed by a secondary addition onto the CO group of the four-membered ring (Schemes 9 and 10).

“…Therefore, in a control experiment, HCl gas was bubbled through a solution of 16 in THF affording 4,4-dimethyl-2-phenyl-1,3-thiazol-5(4H)-one (18) in 73% yield (Scheme 6). The spectroscopic data of 18 were in full agreement with those in [35].…”

mentioning

confidence: 99%

The ‘Azirine/Oxazolone Approach’ to the Synthesis of Aib‐Pro Endothiopeptides

Budzowski

2008

Helvetica Chimica Acta

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The reaction of methyl N‐(2,2‐dimethyl‐2H‐azirin‐3‐yl)‐L‐prolinate (2a) with thiobenzoic acid at room temperature gave the endothiopeptide Bz‐AibΨ[CS]‐Pro‐OMe (7) in high yield. In an analogous manner, (benzyloxy)carbonyl (Z)‐protected proline was transformed into the thioacid, which was reacted with 2a to give the endothiotripeptide Z‐Pro‐AibΨ[CS]‐Pro‐OMe (12). The corresponding thioacid of 7 was prepared in situ via saponification, formation of a mixed anhydride, and treatment with H2S. A second reaction with 2a led to the endodithiotetrapeptide 9, but extensive epimerization at Pro2 was observed. Similarly, saponification of 12 and coupling with either 2a or H‐Phe‐OMe and 2‐(1H‐benzotriazol‐1‐yl)‐1,1,3,3‐tetramethyluronium tetrafluoroborate/1‐hydroxy‐1H‐benzotriazole (TBTU/HOBt) gave the corresponding endothiopeptides as mixtures of two epimers. The synthesis of the pure diastereoisomer BzΨ[CS]‐Aib‐Pro‐AibΨ[CS]‐N(Me)Ph (21) was achieved via isomerization of 7 to BzΨ[CS]‐Aib‐Pro‐OMe (16), transformation into the corresponding thioacid, and reaction with N,2,2‐trimethyl‐N‐phenyl‐2H‐azirin‐3‐amine (1a). The structures of 12 and 21 were established by X‐ray crystallography.