Thiazoles, 5- -, lithiation

Bithiopyrylium dication, 2,2, 6,6 -tetraphenyl-formation, 60, 121 IR and UV spectra, 60, 78 polarography, 60, 96 Biuracils, l,l -linked, photocyclization, photo-cleavage, 55, 142 ( )-Blastmycinone, synthesis via isoxazoline, 60, 301 Blocking groups in metalation reactions, 56, 161 in thiazole lithiation, 56, 223 Borabenzene, see Borin Boracyclobutadiene, calculations, 56, 361,... 

Thieno[2,3 -h]selenophenes lithiation, 4, 950 Thienospirans synthesis, 4, 760 Thieno[3,4-c][l,2,5]thiadiazoles cycloaddition reactions, 6, 534 reactions, 6, 1036 synthesis, 6, 1042, 1044 Thieno[2,3-d]thiazole, 2-acylamino-synthesis, 6, 1010 Thieno[2,3-d]thiazoles synthesis, 5, 116 6, 988, 994 Thieno[3,2-d]thiazoles synthesis, 5, 135 6, 1015 Thieno[3,4-d]thiazolidine-2-thione, perhydro-... 

Lithiated thiazols react with (Ph3P)AuGl to a neutral gold thiazolate, which upon alkylation is transformed into the cationic carbene complex, while the reaction with (tht)AuC6Fs followed by alkylation leads to the neutral complex (Scheme 65).260... 

Silicon protection is also commonly used to direct lithiation chemistry in five-membered heterocycles. For example, oxazoles , thiazoles and Ai-alkylimidazoles ° ° lithiate preferentially at C-2, where the inductive effect of the heteroatoms is greatest. If C-2 is blocked, lithiation occurs at C-5, where there is no adjacent lone pair to destabilize the organolithium. Functionalization of these heterocycles at C-5 can therefore be achieved by first silylating C-2, reacting at C-5 and then removing the silyl group. The synthesis of 666 illustrates this sort of sequence (Scheme 258) °. ... 

A Stille type coupling strategy has been utilised to complete a total synthesis of epothilone E. The vinyl iodide 30 and the thiazole stannane 31 were coupled to give the macrolactone 32 which is a precursor to natural epithilone E. The thiazole stannane 31 was prepared from 4-bromo-2-hydroxymethylthiazole via treatment of the lithiated protected 4-bromO 2-hydroxymethylthiazole with tributylstannyl chloride. This Stille coupling approach was also used to prepare a range of epothilone B analogues <99BMC665>,... 

The hydroboration of alkynylchlorosilanes gave chlorodimethylsilyl-diethylborylalkenes such as 57. The alkene possess two electrophilic centres on the silyl and boryl groups and they react with 2-lithiated thiazoles 58 to give the zwitterionic compound 59 which can drawn as resonance structures 59a or 59b <99JOM98>. 

Syntheses and reactions of lithiated isothiazoles and thiazoles were reviewed. [95H533] Phenylisothiazoles and phenylthiazoles are known to undergo a variety of phototranspositions upon irradiation in benzene solvent. These reactions were reinvestigated. [94JA2292]... 

Methyltetrazole is lithiated in the 5-position, but 1-phenyltetrazole is prone to decompose under the same conditions (71CJC2139). 3,4-Disub-stituted-2-3//-thiazolthiones (7.72) can be lithiated in the 5-position (80S800). 2-(2-Thienyl)thiazole (7.73) is lithiated at the 5-position of the thiazole ring (74BSF2099). 

Note Using lithiated thiazoles or benzothiazoles can result in low yields of the carbene complex precursor due to an equilibrium between the cyclic and acyclic forms [59] (see Figure 6.19). 

Treatment of thiazole and benzothiazole with a lithium hase results in selective deprotonation at C-2. The metallation of thiazole ring carbons has been discussed in great detail in CHEC-II(1996) <1996CHEC-11(3)373>. A recent example of the lithiation of thiazole at C-2 used a solution of -butyllithium in hexanes and was carried out in ether at -80 °C (Scheme 20) <2002DOC289>. 

Halomethyl thiazoles are highly useful synthetic intermediates. Many reactions involve abstraction of an acidic halomethyl proton. For example, the transformation of 2-chloromethyl-4-methylthiazole 123 (among other chloro-alkyl thiazoles) into the corresponding epoxide 124 by lithiation with -butyllithium was followed by reaction with the appropriate ketone (Scheme 45) <2003T1381>. 

Thiazolines activated with an equivalent of BF3 readily react with a wide range of organometals, giving tranj-4,5-disubstituted thiazoles stereoselectively. Alkyllithiums, Grignard reagents, lidiium alkynides, nitronates, ester and ketone enolates have been employed as the nucleophile. Stereocontrolled construction of three contiguous asymmetric centers is performed with a lithiated isothiocyanatoacetate, and the product is successfully transformed to (+)-biotin (Scheme 27), ° ... 

The directed metalation of aromatic systems that was discussed in Section 2.1.3.3 has one ramification that was not mentioned there the directed lithiation of an o-methyl group. Although the resultant species is formally a resonance-stabilized anion, and therefore covered in Volume 2 of this series, we mention it here for consistency with the other topics covered. In particular, the examples that have appeared in recent years involve substrates having a methyl ortho to a tertiary amide. Intentional use of such a directed lithiation has been used in the synthesis of the isocoumarin natural products hydrangenol and pyllodul-cin.137,138 Interestingly, the directed metalation of 5-methyl-oxazoles and -thiazoles occurs in preference to deprotonation at a 2-methyl group (azaenolate) (Scheme 33). ... 

Lithiation of the methyl derivatives of such five-membered heteroaromatics as pyrrole , thiophene , l,3-thiazole ° , 1,3-oxazole , isoxazole , 1,3,4-thiadiazole , 1,3,4-oxadiazole and imidazole also occurs. For the sulfur heterocyclics, ring metallations and ring opening after lithiation are complications. 

For thiazoles, metallation occurs at the 2-position if free but otherwise at the 5-site °. Lithiation of 2-Me derivatives can proceed on the side chain, e.g. ... 

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