Synthesis and Catalytic Properties of 4-Aryl-2,3-dihydro-4H-pyrimido[2,3-b]benzothiazoles for Asymmetric Acyl or Carboxyl Group Transfer Reactions

Abstract

4-Aryl-2,3-dihydro-4H-pyrimido[2,3-b]benzothiazoles (4-Ar-DHPBs) were synthesized and their catalytic activity and selectivity in kinetic resolution of a secondary alcohol as well as in the Steglich rearrangement and related reactions were evaluated. 4-Aryl-DHPBs showed low enantioselectivity in the acylative kinetic resolution of 1-phenylethanol. Conversely, they catalyzed the Steglich rearrangement with moderate to excellent enantioselectivity, demonstrating the possibility for remote stereocontrol by introduction of a substituent at the 4-position of DHPB.

Asymmetric Hydrogenation of β‐Secondary Amino Ketones Catalyzed by a Ruthenocenyl Phosphino‐oxazoline‐ruthenium Complex (RuPHOX‐Ru): the Synthesis of γ‐Secondary Amino Alcohols

“…TheN -benzyl group could be replacedb yN -aromatic substituents while retaining excellent catalytic behavior.E xcellent yields and enantioselectivities were also obtainedw ith regard to N-aromatic substrates possessing para-substituted Ar groups (entries [16][17][18][19][20]. [a] As in Table 1using DBU as abase.…”

“…Alcohol 10 was subsequently transformed to ac hiral bicyclic isothiourea 11,anew class of organic catalyst, in 37% yield and with 85% ee over two steps. [16] Theh ydrogenated product 2l is also au seful intermediatef or the synthesiso f( À)-Paroxetine,at herapeutically importanta ntidepressant. [4] Thus, 2l could be transformedt oc yclic sulfamidate 4 using as imilar method to that described for the synthesiso f9.…”

Isothiourea‐Mediated Asymmetric O‐ to C‐Carboxyl Transfer of Oxazolyl Carbonates: Structure–Selectivity Profiles and Mechanistic Studies

“…[41] It appears that benzannulation of the heterocyclic carbonate leads to only modest enantiocontrol in the isothiourea-mediated rearrangement of these carbonates, consistent with the observations of Okamoto and co-workers. [24] …”

“…[20] Building upon these precedents, and as part of our existing research programme focusing upon Lewis base catalysis, [21] we have shown that isothioureas such as HBTM 11 and 13 promote the asymmetric O-to C-carboxyl rearrangement of oxazolyl carbonates with high enantioselectivity (up to 94 % ee). [22,23] Notably, recent work by Okamoto has probed the ability of a C(4)-stereodirecting unit within tetrahydropyrimidine-derived isothioureas to promote the asymmetric Steglich rearrangement, [24] whereas Grçger and Dietz have utilised isothioureas for related asymmetric O-to Cacetyl transfer processes. [25] To understand the origins of asymmetric induction in the O-to C-carboxyl transfer process using HBTM 11 we have previously carried out molecular modelling calculations, allowing a simple model for asymmetric induction in this process to be developed ( Figure 1).…”

“…In comparison to HBTM 11, the incorporation of an additional syn-configured C(3)-iPr substituent (isothiourea 13) leads to marginally increased stereoselectivities under optimised conditions (Table 1, entries [18][19][20][21][22], with the incorporation of an electronegative Cl atom within the benzothiazole unit (isothiourea 18) giving negligible change in stereoselectivity ( Table 1, entry 23). The inclusion of alternative C(2)-2-naphthyl or C(3)-methyl units (within 19 and HBTM 2 12 respectively) gave slightly lower enantioselectivities than 13 ( Table 1, entries [24][25][26][27][28]. The effect of both stereochemical and cyclic constraints were also investigated, with tetracyclic syn-20 proving highly reactive and enantioselective (Table 1, entries 29-31), whereas the diastereoisomeric isothiourea anti-21 gave no C-carboxylazlactone product, returning mainly starting material and about 10 % azlactone (Table 1, entries 32-34).…”