Guide to enantioselective dirhodium(II)-catalyzed cyclopropanation with aryldiazoacetates

Abstract

Catalytic enantioselective methods for the generation of cyclopropanes has been of longstanding pharmaceutical interest. Chiral dirhodium(II) catalysts prove to be an effective means for the generation of diverse cyclopropane libraries. Rh2(R-DOSP)4 is generaally the most effective catalyst for asymmetric intermolecular cyclopropanation of methyl aryldiazoacetates with styrene. Rh2(S-PTAD)4 provides high levels of enantioinduction with ortho-substituted aryldiazoacetates. The less-established Rh2(R-BNP)4 plays a complementary role to Rh2(R-DOSP)4 and Rh2(S-PTAD)4 in catalyzing highly enantioselective cyclopropanation of 3- methoxy-substituted aryldiazoacetates. Substitution on the styrene has only moderate influence on the asymmetric induction of the cyclopropanation.

Design and Synthesis of Novel Chiral Dirhodium(II) Carboxylate Complexes for Asymmetric Cyclopropanation Reactions

“…[4] [Rh 2 (S-PTAD) 4 ]d emonstrated enhanced levelso fe nantioselectivitya nd acted as ac omplementaryc atalyst when [Rh 2 (S-DOSP) 4 ]f ailed to give high asymmetrici nduction with someo fd onor-acceptor systems. [5] In addition, [Rh 2 (S-PTAD) 4 ]w as reportedt ob et he optimal chiral catalyst whent he acceptor group in the donor-acceptor substratesi sap hosphonate ester, [4] nitrile, [6] trifluoromethyl [7] or keto [8] group,g iving better enantioselectivities than [Rh 2 (S-PTTL) 4 ]. In fact, the emergence of [Rh 2 (S-PTAD) 4 ]c ircumvented to ag reat extent the limitations of selectivity associated with [Rh 2 (S-DOSP) 4 ].…”

“…Methyl (E)-1-(p-methoxyphenyl)-2-phenylcyclopropanecarboxylate (17): [5] Colourless oil; R f = 0.52 (ethyl acetate/n-hexane, 1:4); Ar-H), 3.74 (s, 3H;C H 3 ), 3.68 (s, 3H;C H 3 ), 3.09 (dd, J = 9.2, 7.6 Hz, 1H;C H), 2.14 (dd, J = 9.2, 4.8 Hz, 1H;C H 2 ), 1.84 ppm (dd, J = 7.2, 4.8 Hz, 1H;C H 2 ). The spectroscopic data are consistent with previously reported data.…”

“…The spectroscopic data are consistent with previously reported data. [5,32] The enantiomeric excess was determined by chiral HPLC (Chiralcel OJ column, 25 0.46 cm, 0.5 %2 -propanol in n-hexane (v/v %);1 mL min À1 , 220 nm, t 1 = 14 min, t 2 = 20 min).…”

On the Structure of Chiral Dirhodium(II) Carboxylate Catalysts: Stereoselectivity Relevance and Insights

“…Accordingly, they introduced Rh 2 (S-PTAD) 4 catalyst which is derived from L-adamantylglycine ligands (Scheme 6b) [37]. As expected, this catalyst succeeded to afford enantioselectivity levels superior to Rh 2 (S-PTTL) 4 in different asymmetric transformations [37,88,[91][92][93][94][95]. For example, Rh 2 (S-PTAD) 4 -catalyzed cyclopropanation of styrene with α-diazobenzylphosphonate resulted into the generation of the corresponding cyclopropylphosphonate product in high levels of enantioselectivity (99% ee) compared to Rh 2 (S-DOSP) 4 (34% ee), Rh 2 (S-biTISP) 2 (88% ee) and Rh 2 (S-PTTL) 4 (97% ee) (Scheme 6b) [37].…”

“…For example, Rh 2 (S-PTAD) 4 -catalyzed cyclopropanation of styrene with α-diazobenzylphosphonate resulted into the generation of the corresponding cyclopropylphosphonate product in high levels of enantioselectivity (99% ee) compared to Rh 2 (S-DOSP) 4 (34% ee), Rh 2 (S-biTISP) 2 (88% ee) and Rh 2 (S-PTTL) 4 (97% ee) (Scheme 6b) [37]. in different asymmetric transformations [37,88,[91][92][93][94][95]. For example, Rh2(S-PTAD)4-catalyzed cyclopropanation of styrene with α-diazobenzylphosphonate resulted into the generation of the corresponding cyclopropylphosphonate product in high levels of enantioselectivity (99% ee) compared to Rh2(S-DOSP)4 (34% ee), Rh2(S-biTISP)2 (88% ee) and Rh2(S-PTTL)4 (97% ee) (Scheme 6b) [37].…”