Sulfonylamino acids

The appropriate aromatic or heteroaromatic substrate 515 was reacted with excess chlorosulfonic acid to yield the sulfonyl chloride 516, which was condensed with an amino acid in aqueous THF-triethylamine to give the sulfonylamino acid 517. THF was discovered to be the optimum solvent for the reaction. The amino acids employed included glycine, L-alanine, DL-valine, l-leucine, L-phenylalanine, L-tyrosine and L-proline. 

4- Dichlorobenzoic acid by treatment with chlorosulfonic acid, as described in ref 273, afforded the 5-sulfonyl chloride, which was converted into a similar 

Some novel cinnamoyImorpholine-4-sulfonylamino acids were similarly prepared starting from cinnamoylmorpholine-/ -sulfonyl chloride 524 (prepared by chlorosulfonation of cinnamoylmorpholine as described in ref. 286). The sulfonyl chloride 524 was used to obtain the corresponding cinnamoylmorpholine sulfonylamino acids, methyl esters, hydrazides and the dipeptide methyl esters.  

4-Chlorocinnamanilide, by warming with chlorosulfonic acid (12 equivalents) as described in ref 336, afforded the 4 -sulfonyl chloride 525. This was converted into the 4-chlorocinnamanilide-4 -sulfonylamino acids, methyl esters, hydrazides and dipeptide methyl esters.  

Thiophene-2-carboxanilide and its /7-chloro and p-bromo derivatives reacted smoothly with excess chlorosulfonic acid (six equivalents) at 40 C to yield the corresponding sulfonyl chlorides 526-528. The thiophene sulfonyl chlorides were used to prepare the corresponding sulfonylamino acids, methyl esters and hydrazides. The sulfonylamino acids were also coupled with the appropriate amino acid methyl esters to form the sulfonamino dipeptide methyl esters.  

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FMOC-protected amino acid fluorides afford the expected Reissert adducts 160 with a good stereoselectivities, the a-sulfonylamino acid fluorides undergo cycliza-tion to adduct 161 [47, 140, 141], Itho s protocol is amenable to using silyl enol ethers 157 as nucleophiles [142], Gibson has used bulky asymmetric acid chlorides as substrates in a Reissert reaction with TMS-CN the corresponding Reissert compound was then treated with aldehydes and sodium hydride to obtain the enantiopure adducts 4 (Scheme 3) [143],... 

Itsuno et al. explored the possibility of using polymer-supported chiral Lewis acids in a model Diels-Alder reaction of methacrolein with cyclopentadiene [23a]. By using an insoluble polymer-supported Lewis acid [23], prepared from borane with cross-linked polymers with a chiral moiety such as an A-sulfonylamino acid, the Diels-Alder adduct is obtained in good yield with almost perfect exo selectivity and moderate enantioselectivity (Eq. 23). 

During recent years, the homogeneous Lewis acid-catalyzed asymmetric Diels-Alder reactions and hetero-Diels-Alder (HDA) reactions have each undergone extensive study. Various chiral Lewis acids including aluminum, titanium or boron, and chiral ligands such as chiral amino alcohols, diols, salen, bisoxazoline or N-sulfonylamino acids have been used as the catalysts [84]. Much efforts have also been made in the investigation of heterogeneous diastereoselective Diels-Alder reactions. 

The catalyst was synthesized from borane dimethyl sulfide and a chiral polymer 103 bearing N-sulfonylamino acid groups. The latter was prepared by co-polymerization of chiral sulfonamide 104 with styrene 58 and the cross-linking agent 105 in the presence of benzoyl peroxide as a radical initiator. 

Most of these supported catalysts contain nitrogen as ligands such as Box, aminoalcohol, N-sulfonylamino acid and salen. 

Itsuno synthesized supported aminoalcohols 111-113 (Scheme 57) [104] and N-suUbnylamino acid 114 [105-107] (Scheme 58) by radical suspension copolymerization of the corresponding monomer chiral styryl aminoalcohols and styryl sulfonylamino acid derivatives with styrene and eventually with a crosslinker. 

Supported Aminoalcohol and A-Sulfonylamino Acid-Derived Oxazaborolidine or Oxazaborolidinone... 

The styryl chiral sulfonylamino acid derived from L-valine 114a, L-isoleucine 114b, L-threonine 114c or D-2-phenylglycin 114d (Scheme 58). The loading of aminoacid residue was about 0.78-0.88 mmol/g for a polymer formed with 10% of the styryl chiral sulfonylamino acid, 80% styrene and 10% of DVB with a yield range of 85-96%. In the case of valine, for a polymer formed with 50% of the styryl chiral sulfonylamino acid, 40% styrene and 10% of DVB, it could be up to 2.55 mmol/g and 73% yield [105]. 

The Diels-Alder reaction was performed with cyclopentadiene and methacroleine (Scheme 56) in presence of 15 mol% of the oxazaborolidine and oxazaborolidinone catalysts derived respectively from supported aminoalcohols and from V-sulfonylamino acid polymers. The oxazaborolidine and oxazaborolidinone catalysts were formed in situ by action of BH3, BH2Br, BHBr2 or BBrs. The diastereoselectivity was excellent in favour of the exo adduct and yields from 65 to 99%. It is noteworthy that higher loading of chiral catalyst site in the polymer, lower exo selectivity and enantioselectivity. The diastereoselection depended not only on the nature of the supported ligand, the crosslinker but also on the borane and the solvent. Results are summarized in Table 6. 

V-sulfonylamino acid resin (15) was prepared fromPS-S02Cl as a chiral catalyst for the asymmetric Diels-Alder reaction of cy-clopentadiene with methacrolein (eq 18). Although resin 15 prepared from PS-SO2CI showed very low enantioselectivity (1 % ee), similar resins prepared from preformed chiral monomers showed much improved selectivity (57-65% ee). ... 

Since our group (22) and Hehnchen s (23) independently announced a new class of chiral acyloxyboranes derive from iV-sulfonylamino acids and borane THF, chiral 1,3 -oxazaborolidines, their utility as chiral Lewis acid catalysts in enantioselective synthesis has been convincingly demonstrated (2(5). In particular, Corey s tryptophan-derived chiral oxazaborolidines 10a and 10b are highly effective for not only Mukaiyama aldol reactions (24) but also Diels-Alder reactions (25). More than 20 mol% of 10b is required for the former reaction, however. Actually, the reaction of the trimethylsilyl enol ether derived from cyclopentanone with benzaldehyde afforded the aldoI products in only 71% yield even in the presence of 40 mol%of 10b (24). We recently succeed in renewing 10b as a new and extremely active catalyst lOd using arylboron dichlorides as Lewis acid components (2(5). 

El-Sayed and co-workers " have extensively studied the chemistry and antimicrobial properties of various sulfonylamino acids and their derivatives. The procedure for the synthesis of these compounds is summarized in Scheme 16. 

The corresponding sulfonylamino acid methyl esters 518 were prepared by treatment of the sulfonylamino acids 517 with absolute methanol-pure thionyl chloride at low temperature (—5 °C to —10 °C). The esters 518, by hydrazinolysis with hydrazine hydrate, afforded the hydrazides 519. The sulfonylamino acids 517 were coupled with the appropriate amino acid methyl ester hydrochloride in THF-water-triethylamine mixture using DCC as the coupling reagent to yield the corresponding sulfonylamino dipeptide methyl esters 520 (Scheme 16). The synthetic sequence depicted in Scheme 16 has been successfully applied to a number of different aromatic sulfonyl chlorides as illustrated by the following examples. 

Many of the sulfonylamino acids and their derivatives showed moderate antimicrobial activity the hydrazides were generally less active. 

Kaml995 Kamahori, K., Tada, S., Ito, K. and Itsuno, S., Synthesis of Polymer-Supported Chiral N-Sulfonylamino Acids and Their Use in Asymmetric Diels-Alder Reaction of Cyclopentadiene with Methacrolein, Tetrahedron Asymmetry, 6 (1995) 2547-2555. 

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