Enantiomerenreine homoallylische Alkohole wie 1 (einfach aus einem (Alk‐2‐enyl)metallreagens mit (−)‐ oder (+)‐Menthon erhältlich) fungieren als Alk‐2‐enyldonoren für Aldehyde. Die Allylübertragung, die über einen sesselförmigen sechsgliedrigen Ring als Übergangszustand verläuft, liefert die α‐Addukte der homoallylischen Alkohole, 2, in guter Ausbeute mit >99 % ee. pTSA=p‐Toluolsulfonsäure.
A highly enantioselective (2Z)-alk-2-enylation of aldehydes was successfully achieved by an allyl-transfer reaction from a chiral allyl donor, which was easily obtained by separation of a diastereomeric mixture of the corresponding homoallylic alcohol gamma-adducts derived from (+)-isomenthone with alk-2-enylmagnesium chloride. [reaction: see text]
The enantioselective allylation of aldehydes to prepare optically pure homoallylic alcohols is one of the most attractive and popular methods for the construction of stereogenic centers [Eq. (1)]. [1, 2d] Not only can this type of reaction provide homoallylic alcohols with high enantiomeric purity, it can also provide modified chiral building blocks after suitable functionalization of the C À C double bond in the introduced allylic unit.Highly enantiopure homoallylic alcohols have been prepared by using allylic organometallic reagents (MCH 2 CH¼CH 2 ; M = metal) and a stoichiometric amount of a chiral auxiliary [3] or a catalytic amount of a chiral promoter. [4] Furthermore, allylation reactions with g-substituted organometallic reagents 4 in the presence of a chiral auxiliary or catalyst afford the g adduct 5 diastereo-and enantioselectively. [5] This CÀC-bond-formation reaction is particularly useful for the construction of vicinal stereogenic centers in a flexible hydrocarbon chain [Eq. (2)].However, to the best of our knowledge, no asymmetric alk-2-enylation reaction (e.g. crotylation) of aldehydes to give 4-substituted homoallylic alcohols 6 (a adduct) has yet been reported [Eq. (3)]. This is because the allylation reactions by alk-2-enyl metal reagents 4 proceed, without exception, with allylic transposition via a six-membered cyclic transition state, affording exclusively the g adduct 5. [6] Recently we discovered an efficient and stereoselective nucleophilic alk-2-enylation reaction of aldehydes that produces the desired a adduct 6. In this procedure, no allylic metal nucleophiles are involved, and a homoallylic alcohol 7 acts as an allyl donor. This unusual allylation reaction appears to proceed through a 2-oxonium [3,3] sigmatropic rearrangement, as shown in Scheme 1. [2a] The acid-catalyzed reaction of aldehyde 1 with the homoallylic alcohol (g adduct) 7 stereoselectively gave the homoallylic alcohol a adduct 6 by an allyl transfer from 7 via hemiacetal (H 1 ) and oxonium cations T 1 and T 2 .More importantly, the Sn(OTf) 2 -catalyzed (10 mol %) reaction of 3-phenylpropanal (1 a) with optically pure allyl donor (3R,4S)-1-phenyl-4-methylhex-5-en-3-ol (5 a; > 99 % ee) gave (3S)-1-phenylhept-5-en-3-ol (6 a) in 85% yield with > 98 % ee (Scheme 2). [2b,c]
Coronavirus disease 2019 (COVID-19) pandemic poses a threat to human beings and numerous cases of infection as well as millions of victims have been reported. The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (RBD) to human angiotensin converting enzyme 2 (hACE2) is known to promote the engulfment of the virus by host cells. Employment of flavor/fragrance compositions to prevent SARS-CoV-2 infection by inhibiting the binding of viral RBD (vRBD) to hACE2 might serve as a favorable, simple, and easy method for inexpensively preventing COVID-19, as flavor/fragrance compositions are known to directly interact with the mucosa in the respiratory and digestive systems and have a long history of use and safety assessment. Herein we report the results of screening of flavor/fragrance compositions that inhibit the binding of vRBD to hACE2. We found that the inhibitory effect was observed with not only the conventional vRBD, but also variant vRBDs, such as L452R, E484K, and N501Y single-residue variants, and the K417N+E484K+N501Y triple-residue variant. Most of the examined flavor/fragrance compositions are not known to have anti-viral effects. Cinnamyl alcohol and Helional inhibited the binding of vRBD to VeroE6 cells, a monkey kidney cell line expressing ACE2. We termed the composition with inhibitory effect on vRBD-hACE2 binding as “the molecularly targeted flavor/fragrance compositions”. COVID-19 development could be prevented by using these compositions with reasonable administration methods such as inhalation, oral administration, and epidermal application.
Enantioselective syntheses
Enantioselective syntheses O 0031 A Novel Enantioselective (2Z)-Alk-2-enylation of Aldehydes via an Allyl-Transfer Reaction from Chiral Allyl Donors Prepared from (+)-Isomenthone.-Chiral allyl donors (III) undergo an allyl transfer to aldehydes (V) in the presence of TosOH as catalyst to give (Z)-homoallylic alcohols in good yields with >99% enantioselectivity. It is assumed that (S)-epimeric donors (IV) will give the corresponding (E)-configurated alcohols. -(NOKAMI*, J.; NOMIYAMA, K.; SHAFI, S. M.; KATAOKA, K.;
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