2021 NJC H3 Chemistry P1 Question Paper Insert

[Turn over NATIONAL JUNIOR COLLEGE SH2 PRELIMINARY EXAMINATION Higher 3 CANDIDATE NAME SUBJECT CLASS REGISTRATION NUMBER CHEMISTRY Paper 1 INSERT 9813/01 Friday 17 September 2021 2 hours 30 minutes INSTRUCTIONS This insert contains information for Question 1. Do not write your answer on the insert. This document consists of 3 printed pages and 1 blank page.

NJC/H3 Chem Prelim/01/2021 2 Information for Question 1 Domino reactions are processes where two or more consecutive reactions occur subsequently in a single reaction vessel without intermediate extraction and purification. Asymmetric domino reactions can be achieved through the use of organic catalysts (also known as organocatalysts). The following extract is one of such synthetic methodologies. Abstract 1 (Angew. Chem., 2007, 46(48), 9202-5) Asymmetric synthesis of complex molecules containing multiple stereocentr es is a well -known research area used for the synthesis of a variety of natural products and other molecules of interest. One of the most important goals in this area is the generation of more than one bond in a multistep reaction concomitant with the creation of multiple stereocentres in a one-pot fashion. In the course of our efforts to develop organocatalytic methodologies to gain rapid access to complex molecules, we recently achieved the synthesis of cyclohexenals containing three contiguous stereocentres in good yields and excellent stereoselectivities by using a multicomponent reaction. In fact, it has been demonstrated with this and other examples that organocatalysis can be a very valuable tool for controlling diverse asymmetric syntheses. Herein we describe the first one -pot asymmetric formation of five stereocentres by an intermolecular two -component reaction, which leads in this particular case to the formation of highly substituted optically active cyclohexanols under room temperature. The optically active cyclohexanols arising from this domino process constitute valuable chiral building blocks since they contain the b -amino alcohol functional motif which is ubiquitous in biologically active compounds. Figure 1 Proposed mechanism for the organocatalyzed asymmetric nitro-Michael/Henry domino reaction.

NJC/H3 Chem Prelim/01/2020 3 Table 1 Screening of the organocatalytic nitro -Michael/Henry reaction of α,β –unsaturated aldehyde 1 with dinitro compound 2, compound 3 and 1,4-diazabicyclo[2.2.2]octane (DABCO) . These reactions are done under room temperature and pressure. Entry Solvent R[a] R1 R2 Yield of isolated major stereoisomer [%] %e.e. 1 CH3CH(OH)CH3 TMS CH2CH3 C6H5 n.d.* 80 2 CH3COOCH2CH3 TMS CH2CH3 C6H5 n.d.* 80 3 HCON(CH3)2 TMS CH2CH3 C6H5 n.d.* 46 4 CHCl3 TMS CH2CH3 C6H5 n.d.* 80 5 CH2Cl2 TMS CH2CH3 C6H5 45 90 6 CH2Cl2 H CH2CH3 C6H5 n.d.* –58** 7 CH2Cl2 TES CH2CH3 C6H5 41 89 8 CH2Cl2 TBDMS CH2CH3 C6H5 35 93 *n.d. = not determined **Opposite enantiomer obtained [a]TMS: –Si(CH3)3, TES = –Si(CH2CH3)3, TBDMS = –Si(CH3)2C(CH3)3)

NJC/H3 Chem Prelim/01/2021 4 Blank Page