Pyrrolidines 1- oxides, rearrangement

The Meisenheimer-type rearrangement of 1-substituted pyrrolidine 1-oxides gives tetrahydro-2//-1,2-oxazines (113 — 114). 

Allylthiols376 and unsaturated lithio sulfones377 have been found to react as nucleophiles with nitrones to yield intermediate hydroxylamines which undergo reverse-Cope cyclization to provide 1,3-thiazolidine N-oxides and pyrrolidine A-oxides, respectively. In the case of derivatives of C-phenyl nitrone (321 R2 = Ph), thermolysis was found to result in smooth Meisenheimer rearrangement leading to 1,5,2-oxathiazinane (322) (see Scheme 76). 

Carbon-13 n.m.r. spectroscopy has been used to study benzylisoquinoline and tetrahydroisoquinoline alkaloids and their JV-methyl quaternary salts.30 N-Benzylpapaverinium bromide has been shown to undergo aerial oxidation in alkaline solution to 2-benzyl-6,7-dimethoxyisoquinolone and to give bases of general structure (10) with methylamine, benzylamine, and pyrrolidine.31 Chlorosulphonation of papaverinol affords the sulphonic acid ester (11), mild hydrolysis of which yields the acid (12), which with diazomethane is esterified and dehydrated to (13).32 N-Methyl-l,2-dihydropapaverine has been shown by kinetic studies and orbital-symmetry requirements to rearrange to the salt (14) by the route previously postulated.33... 

The Meisenheimer-type rearrangement of 1-substituted pyrrolidine 1-oxides 157 gives tetrahydro-2/7-l,2-oxazines 158 (Scheme 79). The -lactam 159 undergoes ring expansion to give 1,2-oxazinone 160 (Scheme 80) <2005EJ01680, CHEC-III(8.04.10)364>. 

Asymmetric rearrangement of cyclohexene oxide Cyclohexene oxide is rearranged to (S)-2-cyclohexene-l-ol in 92% ee by the chiral lithium amide (2) prepared from n-butyllithium and 1. Several related (S)-2-(disubstituted aminomethyl)pyrrolidines prepared from (S)-proline are almost as stereoselective.3... 

The addition of allylamine to the benzaldehyde nitrone 17 gave mainly the //wi.v-3,6-disubs tituted 1,2,5-oxadiazinane 20 via the cyclization of the ci.y-unsaturated hydroxylamine 18 to give the pyrrolidine A-oxide 19, and a final rearrangement step77. The product 20 was relatively sensitive to chromatographic purification, but could be converted to the more stable A -Boc and iV-(4-ni-trobenzoyl) derivatives (X-ray). 

A reversed 2,3 4,5 rearrangement (see Section 1.6.3.1.2.2.2.7. p 3621) is also realized in the rearrangement of pyrrolidine disulfides, which are prepared by inter- or intramolecular oxidative coupling of pyrrolidinethiones 1057. The stereoselectivity of these reactions is extremely high the i7/-diastereomer is the only product isolated in a number of examples, e.g., formation of 2 from 1 and 4 from 3. 

The aromatization of pyrrolidines to 2H-pyrroles occurs in good yields without sigmatropic rearrangement to give l//-pyrroles, which can occur under conditions employing other oxidants such as Mn02 and chloranil (eq 25). ... 

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