The stereochemistry of the addition of chlorotitanium enolates of N-acyl oxazolidin-2-ones to 5- and 6- membered N-acyliminium ions

Abstract

A adição estereosseletiva de enolatos de titânio derivados de N-aciloxazolidin-2-onas a ions N-acilimínios de 5-e 6-membros forneceu pirrolidinas 2-substituídas em proporção diastereoisomérica de moderada a boa (5:1-14:1) enquanto diastereosseletividade inferior foi observada na formação das piperidinas 2-substituídas correspondentes. O curso estereoquímico desta reação mostrou ser modulado pela natureza do ion N-acilimínio cíclico (5 ou 6 membros), pela natureza de seu grupo carbamato e do grupo N-acila presente no precursor do enolato. O modelo lk de aproximação parece ser dirigido pela minimização de interações de natureza não-ligante entre o grupo N-acila do enolato de titânio (IV) e os grupos carbamato e metilênico presentes no ion N-acilimínio.The stereoselective addition of chiral and achiral titanium enolates derived from the corresponding N-acyl oxazolidin-2-ones to 5-and 6-membered N-acyliminium ions afforded 2-substituted pyrrolidines in moderate to good diastereoisomeric ratio (5:1 to 14:1) while lower diastereoselection was generally observed in the formation of the corresponding 2-substituted piperidines. The stereochemical outcome was found to be modulated by the nature of the cyclic N-acyliminium ion (5-or 6-membered) and of its carbamate and by the N-acyl group in the enolate precursor. The preferential lk approach seems to be dictated mainly by the minimization of non-bonding interactions between the N-acyl group in the chlorotitanium (IV) enolate and the carbamate and methylene groups in the cyclic N-acyliminium ion.

Stereoselective addition of chiral titanium enolates to 5-substituted five-membered oxocarbenium ions

“…[28][29][30] Furthermore, upon inspection of the 1 H NMR spectra of the 2,5-disubstituted tetrahydrofurans obtained previously, 11 it became apparent that the vicinal coupling constant eing larger in the syn series (9.0-10.0 Hz) than in the anti series (6.0-8.2 Hz) which suggests that these compounds exhibit a conformational preference.…”

“…26 During the course of our study of stereoselective synthesis of 2,5-substituted tetrahydrofurans through nucleophilic addition to five-membered ring oxocarbenium ions, we have reported the stereoselective Lewis acid-promoted allylsilane substitution reaction at the anomeric carbon of -lactol 1a with preparatively useful trans-2,5 selectivity being observed when a more hindered nucleophile was employed (Scheme 1). 27 Taking into account the high facial discrimination displayed by stereochemically defined titanium enolates in aldol reaction 28 and in their addition to cyclic N-acyliminium ions, 29,30 we have previously studied the reactivity of the titanium enolate of chiral oxazolidinones with the chiral oxocarbenium ion derived from 5-substituted--lactol 1a regarding the generation of the stereogenic centers (C-2 and C-2' in Scheme 2). 11 In continuation of our work on the synthesis of trans-2,5-disubtituted tetrahydrofurans, we report here full details of the diastereoselective additions of stereochemically defined titanium enolates of chiral oxazolidinones to cyclic oxocarbenium ions together with the dependence of the diastereoselectivity on the substitution pattern of -lactol and the nature of the R 3 group in the enolate.…”

A concise and stereoselective synthesis of (+/−)-erythro-methylphenidate

“…In this way, a set of available tertiary amines as bases was investigated. In all cases a variable ratio of compounds 2 and 5 was observed ( Table 1, entries [8][9][10][11][12][13][14] and the use of KOt-Bu furnished the compound 5 as a major product (entry 15). Interestingly, the best yield of compound 2 (60%) was achieved when DBU was employed in the absence of a thiophile (Table 1, entry 14) in which thiazolidinone 5 was not isolated.…”

“…3 The activity of Ritalin ® promotes an enhancement of the cognitive performance in both adults and children diagnosed with AD/HD. 4 Although Ritalin ® is available in the market as the racemate, the (2R,2%R)-(+)-threo-methylphenidate has been reported to be up to 38 times 5 more active than (2S,2%S)-(−)-threo-methylphenidate and several racemic [6][7][8][9] and chiral [10][11][12][13] synthesis of threo-methylphenidate were reported previously.…”

Intermolecular Addition Reactions of N-Acyliminium Ions (Part II)¹

“…The reaction of N-Boc-2-ethoxypyrrolidine 309a with the N,O-silylketene acetal, itself prepared in situ by treatment of N-propionyloxazolidin-2-one 367 with trimethylsilyl triflate and triethylamine, provided a 67:33 mixture of the 2-substituted pyrrolidines 368 and 369 in 45% yield (Scheme 150). 98 The 5-methoxyproline derivative 371 reacted with trimethylsilyloxyfuran compounds, themselves generated in situ by treatment of butenolides 370 with trimethylsilyl triflate under basic conditions, in the presence of trimethylsilyl triflate at -78°C to give a mixture of diastereomeric adducts. Addition of an excess amount of trimethylsilyl triflate to these adducts afforded deprotected pyrrolidines 372 as a mixture of four diastereomers (Scheme 151).…”