Thiourea allylic substitution

Very recently, Shi and co-workers [134] demonstrated that the chiral thiourea-phosphine was an efficient catalyst in the enantioselective allylic substitution of BH carbonates using oxazolones as nucleophiles. The reaction catalyzed by 75 afforded the corresponding products in good to excellent yields and enantioselectivities as well as moderate to good diastereoselectivities (Scheme 9.37). 

A highly enantioselective and regioselective allylic substitution of the BH carbonates using nitroalkanes as nucleophiles was developed by Lu and co-workers [135] in the presence of quinidine-derived thiourea catalyst 76. The nitroalkanes was added to the BH carbonates in the 3 position (as depicted in Scheme 9.36) in good yields and enantioselectivities (Scheme 9.38). 

Based on the enantioselective Michael addition/ISOC (intramolecular silyl nitronate olefin cycloaddition)/lragmentation sequence previously developed by the group of Rodriguez [33a], Shao and coworkers proposed an extrapolation for the construction of spirooxindoles catalyzed by a bifunctional tertiary amine-thiourea catalyst XV between 4-allyl-substituted oxindoles 63 and nitrostyrenes 64 (Scheme 10.21) [33b]. After the addition of TMSCl and EtgN at -30 C, the Michael adduct underwent an ISCX3 to afford the spiro oxime derivatives 65 in very good yields (85-85%), and excellent diastereo (up to >30 1) and enantioselectivities (94-99% ee) after the treatment with TBAF. 

Morita-Baylis-Hillmann carbonates were involved in an asymmetric allylic substitution reaction with diphenylphosphine oxide in the presence of chiral thiourea-phosphine organocatalysts. The enantioselectivity was > 96% (Scheme 28). ... 

The asymmetric allylic substitution reaction of Morita-Baylis-Hillman carbonates (226) with diphenyl phosphite in the presence of chiral multifunctional thiourea-phosphine catalyst (228) provided allylic phosphites (227) in high yields and with excellent enantioselectivities (Scheme 76). 

In contrast to the above additions A-allyl- and substituted A-allyl-amides, -urethanes, -ureas and -thioureas undergo intramolecular cyclization only in 6(3-96% sulfuric acid to give the corresponding oxazolinium and thiazolinium salts. Treatment of these cations with base yields 2-oxazolines and 2-thiazolines in moderate to good yields. The reaction is illustrated by the conversion of A-2-phenylallylacetamide (342) into 2,5-dimethyl-5-phenyl-2-oxazoline (343) in 70% yield 70JOC3768) (see also Chapter 4.19). 

Scheme 6.23 Claisen rearrangement of a 2-alkoxycarbonyl substituted allyl vinyl ether in the presence of thiourea derivative 9.

The asymmetric alcoholytic ring opening of 4-substituted-2-phenyl-4,5-dihydro-l,3-oxazin-6-ones proved to be a efficient method for the preparation of enatiomerically pure /3-amino acid derivatives <2005AGE7466>. Treatment of 2,4-diphenyl-4,5-dihydro-l,3-oxazin-6-one 208 in the presence of the bifunctional chiral thiourea catalyst 211 resulted in formation of an enantiomerically enriched mixture of the unchanged oxazinone (iJ)-208 and allyl (4)-3-benzoyl-amino-3-phenylpropanoate 209. The resolved material (iJ)-208 and the product 209 could easily be separated by a selective hydrolytic procedure that converted oxazinone (iJ)-208 quantitatively into the insoluble iV-benzoyl /3-amino acid 210 (Scheme 37). 

Nagasawa and co-workers reported the use of a chiral bis-thiourea catalyst (108) for the asymmetric MBH reactions of cyclohexenone with aldehydes [95]. Since others had already shown that thioureas form hydrogen bonds with both aldehydes and enones, it was hypothesized that the inclusion of two thiourea moieties in close proximity on a chiral scaffold would organize the two partners of the MBH reaction and lead to enantiofacial selectivity. Initial studies showed that the achiral 3,5-bis-(trifluoromethyl)phenyl-substituted urea increased the rate of MBH reaction between benzaldehyde and cyclohexenone. These authors then showed that chiral 1,2-cyclohexyldiamine-linked bis-thiourea catalyst 108, used at 40 mol% loading in the presence of 40 mol% DMAP, promoted the MBH reactions of cyclohexenone with various aliphatic and aromatic aldehydes (40) to produce allylic alcohols in moderate to high yields (33-99%) and variable enantio-selectivities (19-90% ee Table 6.33). 

Like other acid chlorides and cyanogen bromide, vinyl chloroformate brings about fission of benzylic and allylic amines e.g. hydrastine is converted into the enol lactone (145).169 Normorphine and norcodeine give substituted thioureas (146) with alkyl isothiocyanates.170... 

Equation (at) is the more general, as more substitution is tolerated on starting material LXXXIII than on LXXXII. Yields are good to excellent. Starting material LXXXIII is accessible in a facile procedure from allylic halide, 1,1,3,3-tetramethyl-thiourea, [S=C(NMe2)a], and a salt, e.g., [NHJCIO4, K[PFJ, etc. . 

N-substituted compounds such as phenyl-, acetyl- or allyl-thiourea in 0.5 to 1% concentration give composites with excellent color stability. However, the biocompatibility of these compounds has not been established. 

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