Palladium- and Copper-Catalyzed Aryl Halide Amination ...

More documents

Recommendations

Info

18 J. E. R. Sadig, M. C. Willis REVIEW haloaryl) ketone substrates previously used in benzofuran synthesis (see Scheme 49). 122 4 Carbon–Sulfur Bond Formation Relative to the carbon–nitrogen and carbon–oxygen bond-forming reactions discussed above, there are far fewer examples of catalytic aryl carbon–sulfur bondforming processes in the literature. However, reactions are beginning to be developed that exploit the highly nucleophilic character of thiols (and related functional groups) and synthetically useful methods with very low catalyst loadings are being reported. 123 The number of applications of these reactions to the synthesis of heterocycles is also growing. 4.1 Benzothiophenes Although a number of metal-catalyzed benzothiophene syntheses exist, 1,2 few of these involve a key carbon–sulfur bond formation using an aryl halide substrate. As discussed in section 3.1, Willis et al. demonstrated the use of a palladium-catalyzed intramolecular O-enolate arylation in the synthesis of benzofurans (see Scheme 49). 106 Similarly, the same group showed that thio ketones, derived from the same a-(o-haloaryl) ketone substrates using phosphorus pentasulfide, could also undergo this enolization–cyclization, again using a DPEPhos catalyst system to afford benzothiophenes. 106 Scheme 59 shows an aryl bromide example, although the corresponding aryl chloride also underwent cyclization, albeit in a reduced 44% yield. Br S Scheme 59 Pd2(dba)3 (2.5 mol%) DPEPhos (22) (6 mol%) Cs2CO3 S toluene, 100 °C 74% In 2009 Lautens and co-workers extended the use of gemdihalovinylanilines in indole synthesis (see Scheme 5) to establish similar thiophenols as precursors for benzothiophenes. 124 The combination of a palladium-catalyzed carbon–sulfur bond-forming reaction with a second cross-coupling process, such as a Suzuki–Miyaura, Heck or Sonogashira reaction, yielded diversely functionalized benzothiophenes. For example, combination of thiophenol 116 with thiophene-3-boronic acid using an SPhos-derived catalyst delivered benzothiophene 117 in 99% yield (Scheme 60). The majority of examples reported involved Suzuki chemistry; a broad range of boronic acids, as well as other boron reagents, were readily included and allowed the introduction of aryl, alkenyl and alkyl C2 substituents. Application of the methodology to a variety of thiophenol backbones afforded the required heterocycles in mostly excellent yields. Synthesis 2011, No. 1, 1–22 © Thieme Stuttgart · New York S Scheme 60 4.2 Benzothiazoles Two research groups have established benzothiazole syntheses based on a key catalytic intermolecular carbon–sulfur bond-forming step. In the first approach, Itoh and Mase utilized a palladium-catalyzed thioetherification of o-bromoanilides using a thiol surrogate coupling partner. 125 For example, reaction between aryl bromide 118 and thiol 119, an odorless thiol surrogate, using a XantPhos-derived catalyst, ultimately delivered benzothiophene 120 in 75% yield (Scheme 61). The reaction proceeded via intermediate sulfide 121, which was cleaved under basic conditions and then cyclized in the presence of acid to generate the aromatic product. p- Methoxybenzylthiol could also be employed as the thiol surrogate, allowing sulfide cleavage under acid conditions. Scheme 61 Br Br SH 116 + B(OH) 2 PdCl2 (3 mol%) SPhos (14) (3 mol%) K 3PO4, Et3N dioxane, 110 °C S 117, 99% 118 121 F + H N O Br Me Pd2(dba)3 (5 mol%) XantPhos (2) (10 mol%) i-Pr2NEt, dioxane reflux F H N S O Me O SH O OR O 119 Me Me NaOEt, THF, r.t. then TFA, reflux S 120, 75% Rather than use a thiol surrogate, Ma and co-workers exploited metal sulfides in copper-catalyzed couplings with o-haloanilides to generate benzothiazoles. 126 They were able to show that sodium sulfide nonahydrate could be coupled with o-iodoanilides, and following acidic workup, deliver the desired benzothiazole products. For o-bromo substrates, the use of potassium sulfide was optimal. Both systems utilized a ligandless copper(I) iodide catalyst; significant variation of the substrate substituents was possible, delivering benzothiazoles in good to excellent yields (Scheme 62). The use of an intramolecular carbon–sulfur bond-forming reaction has proved more popular in the synthesis of benzothiazoles. In 1982, Bowman, Heaney and Smith reported an intramolecular, copper-catalyzed S-arylation in the synthesis of 2-alkyl- and 2-aryl-1,3-benzothiazoles from F N S Me
REVIEW Palladium- and Copper-Catalyzed Heterocycle Synthesis 19 F H N I O Me Na2S CuI (10 mol%) DMF, 80 °C then HCl, r.t. F N S 75% .9H2O + Scheme 62 o-halothioacetanilides and o-halothiobenzanilides, respectively. 127 Castillón and co-workers extended this methodology to a more efficient palladium-catalyzed cyclization of o-bromothioamides (Scheme 63). 128 It was also shown that cyclization of o-bromothioureas, prepared from o-bromophenylisothiocyanates and amines, afforded 2-aminobenzothiazoles under similar reaction conditions (122 → 123). H N S Br 122 Scheme 63 Batey and co-workers reported a comparison of the copper- and palladium-catalyzed syntheses of 2-aminobenzothiazoles based on this same cyclization of obromothioureas. 129 The use of copper catalysis generally led to higher yields and conversions. Both metals were also shown to catalyze an example of a one-pot thiourea formation–cyclization reaction in the same excellent yield. Batey’s research group also demonstrated that cyclization of o-bromothioamides under the same copper(I) iodide/1,10-phenanthroline catalyst system afforded benzothiazoles in excellent yields; 115 a representative example is shown in Scheme 64. Jiang and Ma reported a related copper-catalyzed cyclization employing oxazolidin-2-one as the ligand; a number of aryl chloride substrates were included in their study, and effectively converted into benzothiazoles. 117 Pan and co-workers reported a related preparation of 2-aminobenzothiazoles using a copper(I) iodide/oxazoline catalyst system. 130 Scheme 64 H N Ph + O Br Me Me Me H N NMe 2 S Br H N S Br K 2S CuI (10 mol%) DMF, 140 °C then HCl, r.t. Pd2(dba)3 (5 mol%) JohnPhos (106) (5.5 mol%) Cs2CO 3 dioxane, 80 °C Pd 2(dba) 3 (5 mol%) P(t-Bu)3 (5.5 mol%) OMe Cs2CO 3 dioxane, 80 °C CuI (5 mol%) 1,10-phenanthroline (10 mol%) Cs 2CO3, reflux 88% N S Me Ph N Me Me S Me 88% N S 123, 92% N S 93% NMe 2 OMe The Wu research group described the synthesis of 2-aminobenzothiazoles by the reaction of o-iodobenzamines with isothiocyanates using a copper(I) iodide/phenanthroline catalyst system (Scheme 65). 131 The method was useful as it eliminated the need to generate an ohalobenzothiourea cyclization precursor in a separate step, with the addition/carbon–sulfur coupling reaction occurring in one pot. The authors exploited the method in the preparation of an 18-membered library. F Scheme 65 A number of benzothiazole syntheses that involve tandem processes have also appeared in the literature. Vera and Pelletier utilized tandem palladium-catalyzed carbon– sulfur and carbon–nitrogen arylation reactions to prepare a series of aminobenzothiazoles. 132 For example, the combination of dibromothiobenzamide 124 and isopropylamine, using a JohnPhos catalyst, delivered 4-aminobenzothiazole 125 in 47% yield (Scheme 66). As can be seen from the remainder of the examples in Scheme 66, it was possible to alter the position of the second bromine substituent, to generate 5-, 6-, and 7-amino-substituted products. Scheme 66 NH 2 I + SCN CuI (10 mol%) 1,10-phenanthroline (20 mol%) DABCO toluene, 50 °C 99% Br NHi-Pr 124 i-PrHN H N Ph + H2N(i-Pr) S Br 16% N S Ph Pd 2(dba) 3 (10 mol%) JohnPhos (106) (20 mol%) i-PrHN Patel and co-workers showed that 2-arylthiobenzothiazoles can be accessed from cascade intra- and intermolecular carbon–sulfur bond-forming reactions using a single catalytic system. 133 A combination of o-iodo- or o-bromodithiocarbamates and iodoarenes were subjected to a copper(I) iodide/diamine catalyst system yielding the substituted benzothiazoles in mostly excellent yields (Scheme 67). The methodology was successfully applied to the synthesis of a cathespin-D inhibitor analogue. The same research group developed a cascade protocol for the synthesis of 2-thio- or 2-oxa-benzothiazoles by the copper-catalyzed reaction of o-iodo- or o-bromoarylisothiocyanates with a sulfur or oxygen nucleophile, respectively. 134 The required dithiocarbamates or Synthesis 2011, No. 1, 1–22 © Thieme Stuttgart · New York F Cs 2CO 3, NaOt-Bu toluene-dioxane 80 °C 50% N S Ph N S NH N S 125, 47% N S NHi-Pr 39% Ph Ph
Page 1 and 2: REVIEW 1 Palladium- and Copper-Cata
Page 3 and 4: REVIEW Palladium- and Copper-Cataly
Page 17: REVIEW Palladium- and Copper-Cataly

Palladium- and Copper-Catalyzed Aryl Halide Amination ...

Create successful ePaper yourself

Delete template?

Save as template?