Phosphines with thioesters

A wide range of a,P-unsaturated acceptors work well under standard reaction conditions with pre-catalyst 75c (Table 7). Acceptors include a,P-unsaturated esters, amides, alkyl ketones, and phosphine oxides, many of which provide the products in greater than 90% ee [68, 69], a,P-Unsaturated phenyl ketones, nitriles, and thioesters also work, albeit with lower enantioselectivity. The scope has been extended to include a variety of vinyl phosphonate precursors providing good chemical yields and moderate to high enantioselectivity (entries 9 and 10). 

Tan also found that guanidine 21, acting as a base to activate the o [3], X [3] tautomers of diaryl phosphine oxides, catalyzes the asymmetric phospha-Michael reachon of aryl nitroalkenes (Scheme 5.42) [76]. He later employed 21 to realize highly enantioselective Michael additions of dithiomalonate and 3-keto thioesters with a range of acceptors, including maleimides, cyclic enones, furanone, and acyclic 1,4-dicarbonylbutenes [77]. 

The intramolecular aza-Wittig reaction of azidothioesters provides a new approach to functionalized thiazolines <07AG(E)2701>. Coupling of protected amino acids 79 with azido thiols 80 provides thioesters 81, which are treated with triphenyl phosphine to afford thiazolines 17 in good yields. Similarly, the bis(thioester) 82 is converted into the bis(thiazoline) 19. These thiazolines are readily oxidized to the corresponding thiazoles (vide supra). 

An alternative elegant native ligation approach has recently been proposed where the Staudinger reaction is exploited to couple the carboxy component as a thioester via trans-thioesterification to a suitable phosphine scaffold that reacts with azidoacyl peptides to produce the imino-X, -phosphine. This chemical ligation is followed by nucleophilic attack by the imino-X -phosphine nitrogen on the thioester to form the amide bondt °°l (Section 2.2.1.10). 

Hackenberger and Kleineweischede reported a traceless Staudinger ligation for the head-to-tail macrocyclization of peptides without a deprotection step (Fig. 8) [63]. In this strategy, a phosphine tethered to a thioester at the C-terminus of a peptide reacts intramolecularly with an azide at the N-terminus to form the cyclic peptide. 

The synthesis of branched peptides using masked side-chain thioester derivatives of Asp and Glu which are compatible with Fmoc-SPPS is an important goal. Boll et al. synthesized cyclic and branched chain peptides using bis (2-sulfanylethyl)amido (SEA) side-chain derivatives of Asp and Glu via Fmoc SPPS [77]. The tail-to-side-chain cyclization via an in situ reduction of both acyclic and cyclic disulfides with tris(2-carboxyethyl)phosphine (TCEP) triggered the SEA intramolecular ligation. Glu derivatives cyclized more readily than the Asp analogues and without formation of side products (Scheme 9). 

Ketones from thiolic acid esters. - -Di-ketones. A soln. of the startg. thioester and LiBr in anhydrous acetonitrile treated with bis - (3 - dimethylaminopropyl) phenyl-phosphine, a basic thiophile, stirred and heated 17 hrs. at 70° product. 

The OPs of major commercial interest are esters or thioesters derived from phosphoric acid, phosphonic acid, phosphinic acid or phosphoramidic acid. The mostly used derivatives are phosphates, phosphorothioates (S=) and phosphoro-thioates (i -substituted). The general chemical structure of the OPs is a phosphate center with three ester linkages (Fig. 3.2) (Sogorb and Vilanova 2002 Bigley and Raushel 2013). 

Thioalcohols could also be used as reaction components with l-hydroxy-3-phospholene oxides (7 and 8) xmder MW conditions. It was not a sxuprise that the products were thioesters (17) and not esters (9/10) (Scheme 4) [38]. Hence, indeed the alcohol/thioalcohol is phosphinoylated by reaction with the cyclic phosphinic acid and not the phosphinic acid is alkylated by the alcohol or thioalcohol. Quantum chemical calculations revealed that the esterification with thioalcohols is rather endothermic (48.5kJ/mol) and the enthalpy of activation is rather high (cfl. 145 kj/mol), higher than that is for esterifications ca. 102 kj/mol) [38]. 

Interesting rhodium-catalyzed interconversions were studied between acylphosphine sulfides and acid fluorides, acid thioesters and acid esters. In the first place, diethyl-(4-dimethylaminobenzoyl) phosphine sulfide (A) was reacted with 4-methoxybenzoyl fluoride (B) in the presence of 2 mol% of RhH(PPh3)4 and 4 mol% of TEDPDS in refluxing chlorobenzene. Under such conditions, 70% of the starting materials was recovered and ca. 19%... 

Furthermore, highly stereoselective dithiocarbonylation of propargylic mesylates with thiols and carbon monoxide is attained by the use of tetrakis(triphenyl-phosphine)palladium(O) as the catalyst. This dithiocarbonylation is believed to proceed via allenylpalladium and allenyl thioesters, and the high stereoselectivity may be rationalized by a mechanism where nucleophilic attack of a Pd(0) species on the... 

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