Chemo- and diastereoselective cyclopropanation of allylic amines and carbamates

A highly chemo- and diastereoselective protocol for the cyclopropanation of tertiary allylic amines with Shi’s carbenoid [CF₃CO₂ZnCH₂I] is described. The high levels of diastereoselectivity observed in these reactions may be attributed to chelation of the nitrogen atom to the zinc reagent, which then transfers a methylene unit to the syn-face of the olefin. Furthermore, a stereodivergent protocol for the cyclopropanation of a range of allylic carbamates has been developed, which provides access to both diastereoisomers of the corresponding cyclopropanes with very high levels of diastereoselectivity: cyclopropanation with the Wittig-Furukawa reagent [Zn(CH₂I)₂] proceeds under chelation control to give the corresponding syn-product, whilst reaction with Shi’s carbenoid proceeds under steric control to give the corresponding anti-cyclopropane, in >95:5 dr in both cases.     

Highly regioselective and diastereoselective epoxidation of allylic amines with Oxone

Allylic amines (as their protonated ammonium salts) can be epoxidised with high syn diastereoselectivity and regioselectivity at the proximal alkene in substrates with several double bonds using Oxone. The protonated ammonium cation activates the Oxone by hydrogen bonding, thus promoting the oxidation of groups within the vicinity of the complex.     

Diastereoselective Simmons-Smith cyclopropanations of allylic amines and carbamates

Cyclopropanation of 3-(N,N-dibenzylamino)cyclohexene with either Zn(CH(2)I)(2)(Wittig-Furukawa reagent) or CF(3)CO(2)ZnCH(2)I (Shi's reagent) gives the corresponding syn-cyclopropane as a single diastereoisomer, whilst cyclopropanation of 3-(N-tert-butoxycarbonylamino)cyclohexene with CF(3)CO(2)ZnCH(2)I gives the corresponding anti-cyclopropane exclusively; facile N-deprotection gives access to either diastereoisomer of the trifluoroacetic acid salt of 2-aminobicyclo[4.1.0]heptane.     

Asymmetric Simmons-Smith cyclopropanation of unfunctionalized olefins

This paper describes a promising asymmetric cyclopropanation system for unfunctionalized olefins using readily available dipeptide N-Boc-l-Val-l-Pro-OMe as ligand.     

Catalytic asymmetric Simmons-Smith cyclopropanation of unfunctionalized olefins

This paper describes a catalytic asymmetric cyclopropanation system for unfunctionalized olefins using readily available dipeptide N-Boc-l-Val-l-Pro-OMe (1) as ligand.     

Highly diastereoselective and stereodivergent dihydroxylations of acyclic allylic amines: application to the asymmetric synthesis of 3,6-dideoxy-3-amino-L-talose

Aminohydroxylation of tert-butyl sorbate [tert-butyl (E,E)-hexa-2,4-dienoate] using enantiopure lithium (R)-N-benzyl-N-(α-methylbenzyl)amide and (-)-camphorsulfonyloxaziridine gives tert-butyl (R,R,R,E)-2-hydroxy-3-[N-benzyl-N-(α-methylbenzyl)amino]hex-4-enoate in >99:1 dr. Subsequent dihydroxylation under Upjohn conditions (OsO(4)/NMO) gives tert-butyl (2R,3R,4S,5S,αR)-2,4,5-trihydroxy-3-[N-benzyl-N-(α-methylbenzyl)amino]hexanoate (in 95:5 dr) while dihydroxylation under Donohoe conditions (OsO(4)/TMEDA) proceeds with antipodal diastereofacial selectivity to give the (R,R,R,R,R)-diastereoisomer (in 95:5 dr). The amino triols resulting from these dihydroxylation reactions are useful for further elaboration, as demonstrated by the asymmetric synthesis of 3,6-dideoxy-3-amino-L-talose.     

Trifluoromethylated amino alcohol as chiral auxiliary for highly diastereoselective and fast Simmons–Smith cyclopropanation of allylic amine

Three advantages of a trifluoromethylated amino alcohol auxiliary in the Simmons–Smith cyclopropanation of allylic amines are described. The trifluoromethylated amino alcohol auxiliary reduces unwanted side reactions induced by its acidic, and thus less nucleophilic, hydroxy group. The auxiliary accelerated the reaction rate by its electron-withdrawing effect, and promoted the reaction with excellent diastereoselectivity.     

Highly enantio- and diastereoselective one-pot synthesis of acyclic epoxy alcohols and allylic epoxy alcohols

In this report, we outline a highly enantio- and diastereoselective one-pot method for the efficient synthesis of synthetically useful acyclic epoxy alcohols and allylic epoxy alcohols. Our method takes advantage of a highly enantioselective C-C bond-forming reaction to set the initial chirality. The resulting allylic zinc alkoxide intermediate is then epoxidized in situ using either dioxygen or TBHP in the presence of a titanium tetraalkoxide. Epoxy alcohols with up to three contiguous stereocenters are formed in one pot with excellent enantio- and diastereoselectivity. In cases where the zinc alkoxide intermediates contain two different allylic olefins, the more electron-rich double bond is chemoselectively epoxidized to afford an allylic epoxy alcohol. This method represents a highly efficient, stereoselective, and chemoselective approach to the synthesis of a wide range of useful epoxy alcohol and allylic epoxy alcohol products that were previously difficult to access.     

Highly diastereoselective radical addition to glyoxylate imines of chiral amines without additional heteroatoms

The diastereoselective addition of alkyl radicals to glyoxylate imines of α-alkylbenzylamines has been investigated and it was found that diastereoselectivity improved as the size of the alkyl group increased.     

Highly diastereoselective reductions of N-diphenylphosphinyl imines. Synthesis of axial primary cyclic amines.

The reduction of N-diphenylphosphinyl imines of substituted cycloalkanones with lithium tri-sec-butylborohydride provides highly diastereoselective conversions to protected axial primary amines which are demasked via cleavage with acid.     

Highly diastereoselective allylic azide formation and isomerization. Synthesis of 3(2'-amino)-beta-lactams

The stereoselective anti SN2' attack of NaN3 to 3-alkenyl-3-bromo-azetidin-2-ones gave a mixture of diastereomeric azides in fast equilibrium. The [3,3]-sigmatropic rearrangement of allylic azides occurred with complete stereocontrol, allowing the equilibrium to be directed preferentially toward the (E)- or (Z)-isomer, useful precursors of 3(2'-amino)-beta-lactams. [reaction: see text]     

Catalytic asymmetric cyclopropanation of allylic alcohols with titanium-TADDOLate: scope of the cyclopropanation reaction.

A substoichiometric amount of titanium-TADDOLate complex was effective at catalyzing the cyclopropanation reaction of allylic alcohols in the presence 1 equiv of bis(iodomethyl)zinc. After initial optimization of the catalyst structure, excellent yields and enantiomeric ratios were obtained for 3-aryl- or 3-heteroaryl-substituted allylic alcohols (up to 97:3). Alkyl-substituted allylic alcohols gave modest yields and enantiomeric ratios (up to 87:13) but these compare favorably with those observed with other substoichiometric chiral ligands. The full synthetic scope of the reaction is presented in this paper.     

Highly enantioselective cyclopropanation of trisubstituted olefins

A highly efficient asymmetric cyclopropanation of trisubstituted olefins with methyl diazoacetate has been developed in terms of an elaborate modified chiral bisoxazoline/copper complex as a catalyst. A broad scope of substrates is compatible with this catalyst system, including various trisubstituted olefins bearing different aryl-, fused aryl- and alkyl-substituents, providing an easy access to optically active 1,1-dimethyl cyclopropanes in good yields with excellent diastereo- and enantio-selectivity.     

Highly diastereoselective synthesis of anti-gamma-N-benzylamino-beta-hydroxyphosphonates

The reduction of gamma-N-benzylamino-beta-ketophosphonates derived from readily available amino acids can be carried out stereoselectively with Zn(BH(4))(2) at -78 degrees C to produce the anti-gamma-amino-beta-hydroxyphosphonates.     

Highly diastereoselective aminoalkylation of naphthols with chiral amines mediated by lithium perchlorate solution in diethyl ether

One-pot, three-component, Mannich reaction of naphthols with in situ prepared imines in 5 M ethereal lithium perchlorate at room temperature affords the corresponding aminoalkylated products in high yields with high diastereoselectivities. The process is exemplified by the reaction of 2-naphthol with (R)-1-phenylethylamine and an aromatic aldehyde in concentrated ethereal lithium perchlorate solution, which affords a highly diastereoselective access to the requisite 2-aminoalkylated product.     

Synthesis of configurationally stable allylic sulphoxides via diastereoselective oxidation

Low temperature meta-chloroperbenzoic acid oxidation of allylic sulphide derived from (1S)-10-mercaptoisoborneol proceeds in a completely diastereoselective fashion to afford a configurationally stable allylic sulphoxide. The factors affecting the selectivity of the oxidation and the optical stability of the product are discussed.     

Regio- and diastereoselective addition of allylic thioethers to aldehydes

We have developed a regioselective allylation and a regio- and diastereoselective crotylation of aldehydes with pyridin-2-yl sulfides. In the process, we have also optimized the diastereoselectivity of the addition of crotyl phenyl sulfide to aldehydes.